Development of haemostatic decontaminants for treatment of wounds contaminated with chemical warfare agents. 3: Evaluation of in vitro topical decontamination efficacy using damaged skin

Previous studies have demonstrated that haemostatic products with an absorptive mechanism of action retain their clotting efficiency in the presence of toxic materials and are effective in decontaminating chemical warfare (CW) agents when applied to normal, intact skin. The purpose of this in vitro study was to assess three candidate haemostatic products for effectiveness in the decontamination of superficially damaged porcine skin exposed to the radiolabelled CW agents, soman (GD), VX and sulphur mustard (HD). Controlled physical damage (removal of the upper 100 μm skin layer) resulted in a significant enhancement of the dermal absorption of all three CW agents. Of the haemostatic products assessed, WoundStat™ was consistently the most effective, being equivalent in performance to a standard military decontaminant (fuller's earth). These data suggest that judicious application of haemostatic products to wounds contaminated with CW agents may be a viable option for the clinical management of casualties presenting with contaminated, haemorrhaging injuries. Further studies using a relevant animal model are required to confirm the potential clinical efficacy of WoundStat™ for treating wounds contaminated with CW agents. Copyright © 2017 John Wiley & Sons, Ltd.     

Development of haemostatic decontaminants for the treatment of wounds contaminated with chemical warfare agents. 2: Evaluation of in vitro topical decontamination efficacy using undamaged skin

The risk of penetrating, traumatic injury occurring in a chemically contaminated environment cannot be discounted. Should a traumatic injury be contaminated with a chemical warfare (CW) agent, it is likely that standard haemostatic treatment options would be complicated by the need to decontaminate the wound milieu. Thus, there is a need to develop haemostatic products that can simultaneously arrest haemorrhage and decontaminate CW agents. The purpose of this study was to evaluate a number of candidate haemostats for efficacy as skin decontaminants against three CW agents (soman, VX and sulphur mustard) using an in vitro diffusion cell containing undamaged pig skin. One haemostatic product (WoundStat?) was shown to be as effective as the standard military decontaminants Fuller's earth and M291 for the decontamination of all three CW agents. The most effective haemostatic agents were powder‐based and use fluid absorption as a mechanism of action to sequester CW agent (akin to the decontaminant Fuller's earth). The envisaged use of haemostatic decontaminants would be to decontaminate from within wounds and from damaged skin. Therefore, WoundStat? should be subject to further evaluation using an in vitro model of damaged skin. Copyright © 2014 Crown copyright. Journal of Applied Toxicology © 2014 John Wiley & Sons, Ltd.     

Chemical warfare agent simulants for human volunteer trials of emergency decontamination: A systematic review

Incidents involving the release of chemical agents can pose significant risks to public health. In such an event, emergency decontamination of affected casualties may need to be undertaken to reduce injury and possible loss of life. To ensure these methods are effective, human volunteer trials (HVTs) of decontamination protocols, using simulant contaminants, have been conducted. Simulants must be used to mimic the physicochemical properties of more harmful chemicals, while remaining non‐toxic at the dose applied. This review focuses on studies that employed chemical warfare agent simulants in decontamination contexts, to identify those simulants most suitable for use in HVTs of emergency decontamination. Twenty‐two simulants were identified, of which 17 were determined unsuitable for use in HVTs. The remaining simulants (n = 5) were further scrutinized for potential suitability according to toxicity, physicochemical properties and similarities to their equivalent toxic counterparts. Three suitable simulants, for use in HVTs were identified; methyl salicylate (simulant for sulphur mustard), diethyl malonate (simulant for soman) and malathion (simulant for VX or toxic industrial chemicals). All have been safely used in previous HVTs, and have a range of physicochemical properties that would allow useful inference to more toxic chemicals when employed in future studies of emergency decontamination systems.     

Emergency management of chemical weapons injuries

The potential for chemical weapons to be used in terrorism is a real possibility. Classes of chemical weapons include nerve agents, vesicants (blister agents), choking agents, incapacitating agents, riot control agents, blood agents, and toxic industrial chemicals. The nerve agents work by blocking the actions of acetylcholinesterase leading to a cholinergic syndrome. Nerve agents include sarin, tabun, VX, cyclosarin, and soman. The vesicants include sulfur mustard and lewisite. The vesicants produce blisters and also damage the upper airways. Choking agents include phosgene and chlorine gas. Choking agents cause pulmonary edema. Incapacitating agents include fentanyl and its derivatives and adamsite. Riot control agents include Mace and pepper spray. Blood agents include cyanide. The mechanism of toxicity for cyanide is blocking oxidative phosphorylation. Toxic industrial chemicals include agents such as formaldehyde, hydrofluoric acid, and ammonia.     

Efficacy of an oximate-based skin decontaminant against organophosphate nerve agents determined in vivo and in vitro

Recent Canadian research efforts have been directed towards the development of a reactive skin decontaminant (RSD) lotion active against classical nerve agents and mustard. The formulation presently under study consists of a 1.25 molal solution of potassium 2,3-butanedione monoximate (KBDO) in polyethylene glycol methylether 550. Although this formulation has shown good efficacy, concern has been expressed as to the potential toxicity of the reaction products of KBDO and organophosphate (OP) nerve agents. This report details the high efficacy of this lotion in inactivating OPs as measured by the systemic toxicity of the OP/RSD mixtures in rats. In addition, primary cultures of chick embryo neurons were also used to test the efficacy of the RSD. By relating the anticholinesterase activity in these cultures of the OP/RSD mixture to that of pure OP standards, a sensitive measure of the value of the RSD in inactivating tabun, sarin, soman and VX was obtained. Experiments with all four nerve agents in this in vitro system provided a good correlation with the in vivo data, and also indicated that the inactivation process was time- and agent-dependent and also related to the ratio of OP to RSD.     

The percutaneous absorption of soman in a damaged skin porcine model and the evaluation of WoundStat™ as a topical decontaminant

Purpose: The aim of this study was to evaluate a candidate haemostat (WoundStat?), down-selected from previous in vitro studies, for efficacy as a potential skin decontaminant against the chemical warfare agent pinacoyl methylfluorophosphonate (Soman, GD) using an in vivo pig model.

Materials and methods: An area of approximately 3?cm² was dermatomed from the dorsal ear skin to a nominal depth of 100?µm. A discrete droplet of ¹⁴C-GD (300?µg kg^?1) was applied directly onto the surface of the damaged skin at the centre of the dosing site. Animals assigned to the treatment group were given a 2?g application of WoundStat? 30?s after GD challenge. The decontamination efficacy of WoundStat? against GD was measured by the direct quantification of the distribution of ¹⁴C-GD, as well as routine determination of whole blood cholinesterase and physiological measurements.

Results: WoundStat? sequestered approximately 70% of the applied ¹⁴C-GD. Internal radiolabel recovery from treated animals was approximately 1% of the initially applied dose. Whole blood cholinesterase levels decreased to less than 10% of the original value by 15?min post WoundStat? treatment and gradually decreased until the onset of apnoea or until euthanasia. All treated animals showed signs of GD intoxication that could be grouped into early (mastication, fasciculations and tremor), intermediate (miosis, salivation and nasal secretions) and late onset (lacrimation, body spasm and apnoea) effects. Two of the six WoundStat? treated animals survived the study duration.

Conclusions: The current study has shown that the use of WoundStat? as a decontaminant on damaged pig ear skin was unable to fully protect against GD toxicity. Importantly, the findings indicate that the use of WoundStat? in GD contaminated wounds would not exacerbate GD toxicity. These data suggest that absorbent haemostatic products may offer some limited functionality as wound decontaminants.     

Acute toxicity of some nerve agents and pesticides in rats

Objectives: Highly toxic organophosphorus compounds (V- and G-nerve agents) were originally synthesized for warfare or as agricultural pesticides. Data on their acute toxicity are rare and patchy. Therefore, there is a need for integrated summary comparing acute toxicity of organophosphates using different administration routes in the same animal model with the same methodology. Based on original data, a summary of in vivo acute toxicity of selected V- and G-nerve agents (tabun, sarin, soman, VX, Russian VX) and organophosphates paraoxon (POX) and diisopropyl fluorophosphate (DFP) in rats has been investigated. Materials and methods: Male Wistar rats were exposed to organophosphates in several administration routes (i.m., i.p., p.o, s.c., p.c.). The acute toxicity was evaluated by the assessment of median lethal dose (LD₅₀, mg?kg^?1) 2, 4, and 24 hours post exposure. Results: V-agents were the most toxic presented with LD₅₀ ranged from 0.0082?mg?kg^?1 (VX, i.m.) to 1.402?mg?kg^?1 (Russian VX, p.o.), followed by G-agents (LD₅₀?=?0.069?mg?kg^?1/soman, i.m./ – 117.9?mg?kg^?1/sarin, p.c./), organophosphate POX and DFP (LD₅₀?=?0.321?mg?kg^?1/POX, i.m./ – 420?mg?kg^?1/DFP, p.c./). Generally, i.m. administration was the most toxic throughout all tested agents and ways of administration (LD₅₀?=?0.0082?mg?kg^?1/VX/ – 1.399?mg?kg^?1/DFP/) whereas p.c. way was responsible for lowest acute toxicity (LD₅₀?=?0.085?mg?kg^?1/VX/ – 420?mg?kg^?1/DFP/). Conclusion: The acute toxicity of selected organophosphorus compounds is summarized throughout this study. Although the data assessed in rats are rather illustrative prediction for human, it presents a valuable contribution, indicating the toxic potential and harmfulness of organophosphates.     

Toxicity Assessment of Industrial Chemicals and Airborne Contaminants: Transition from In Vivo to In Vitro Test Methods: A Review

Exposure to occupational and environmental contaminants is a major contributor to human health problems. Inhalation of gases, vapors, aerosols, and mixtures of these can cause a wide range of adverse health effects, ranging from simple irritation to systemic diseases. Despite significant achievements in the risk assessment of chemicals, the toxicological database, particularly for industrial chemicals, remains limited. Considering there are approximately 80,000 chemicals in commerce, and an extremely large number of chemical mixtures, in vivo testing of this large number is unachievable from both economical and practical perspectives. While in vitro methods are capable of rapidly providing toxicity information, regulatory agencies in general are still cautious about the replacement of whole-animal methods with new in vitro techniques. Although studying the toxic effects of inhaled chemicals is a complex subject, recent studies demonstrate that in vitro methods may have significant potential for assessing the toxicity of airborne contaminants. In this review, current toxicity test methods for risk evaluation of industrial chemicals and airborne contaminants are presented. To evaluate the potential applications of in vitro methods for studying respiratory toxicity, more recent models developed for toxicity testing of airborne contaminants are discussed.     

Biological fate of sulphur mustard, 1,1'-thiobis(2-chloroethane): isolation and identification of urinary metabolites following intraperitoneal administration to rat

1. The metabolism of sulphur mustard, 1,1'-thiobis(2-chloroethane), in vivo was investigated following i.p. administration to rat.

2. Approx. 60% of dose was excreted in the 24 h urine. Many metabolites were present; nine have been isolated by h.p.l.c. and characterized by mass spectrometry. Structural assignments were confirmed by comparison with authentic synthetic standards.

3. Some metabolites result from initial hydrolysis of the sulphur mustard, but the majority are formed by conjugation with glutathione. These are further metabolized to N-acetylcysteine conjugates, or to methylthio/methylysulphinyl derivatives by a pathway probably involving β-lyase, accompanied by oxidation of the mustard sulphur atom to sulphoxide or sulphone.

4. Thiodiglycol sulphoxide, 1,1'-sulphonylbis[2-S (N-acetylcysteinyl)ethane] and 1,1'-sulphonylbis[2-methylsulphinyl)ethane] or 1-methylsulphinyl-2-[2-(methylthio ethylsulphonyl]ethane were the most prevalent metabolites resulting from the three major pathways. Metabolic pathways for the formation of the excretion products are proposed.     

Skin decontamination of mustards and organophosphates: comparative efficiency of RSDL and Fuller's earth in domestic swine

Research in skin decontamination and therapy of chemical warfare agents has been a difficult problem due to the simultaneous requirement of rapid action and non-aggressive behaviour. The aim of this study was to compare the performance of two decontaminating systems: the Canadian Reactive Skin Decontaminant Lotion (RSDL) and the Fuller's Earth (FE). The experiment was conducted with domestic swine, as a good model for extrapolation to human skin. RSDL and FE were tested against sulphur mustard (SM), a powerful vesicant, and VX, a potent and persistent cholinesterase inhibitor. When used 5 min after contamination, the results clearly showed that both systems were active against SM (10.1 mg/cm(2)) and VX (0.06 mg/cm(2)). The potency of the RSDL/sponge was statistically better than FE against skin injury induced by SM, observed 3 days post-exposure. RSDL was rather more efficient than FE in reducing the formation of perinuclear vacuoles and inflammation processes in the epidermis and dermis. Against a severe inhibition (67%) of plasmatic cholinesterases induced by VX poisoning, the potencies of the RSDL/sponge and FE were similar. Both systems completely prevented cholinesterase inhibition, which indirectly indicates a prevention of toxic absorption through the skin.     

Organophosphate nerve agent toxicity in Hydra attenuata

The toxicity for analogues of sarin (GB), soman (GD), and VX was evaluated using Hydra attenuata as a model organism. The organophosphate nerve agent analogue simulants used in this investigation included the following: isopropyl p-nitrophenyl methylphosphonate (for GB); pinacolyl p-nitrophenyl methylphosphonate (for GD); and diisopropyl S-(2-diisopropylaminoethyl)phosphorothioate, diethyl S-(2-diisopropylaminoethyl)phosphorothioate, and diethyl S-(2-trimethylaminoethyl)phosphorothioate (for VX). The toxicity of each organophosphate nerve agent was assessed quantitatively by measuring the minimal effective concentration within 92 h in H. attenuata. There is a positive correlation between the molecular hydrophobicity of the compound and its ability to cause toxicity. Results from this study indicate the potential for application of this assay in the field of organophosphate chemical warfare agent detection, as well as for the prediction of toxicity of structurally similar organophosphate compounds. The minimal effective concentration for two of the VX analogues was 2 orders of magnitude more toxic than the analogue for GD and 4 orders of magnitude more toxic than the analogue for GB.     

The percutaneous toxicokinetics of Sulphur mustard in a damaged skin porcine model and the evaluation of WoundStat™ as a topical decontaminant

This study used a damaged skin, porcine model to evaluate the in vivo efficacy of WoundStat™ for decontamination of superficial (non‐haemorrhaging), sulphur mustard‐contaminated wounds. The dorsal skin of 12 female pigs was subjected to controlled physical damage and exposed to 10 μL ¹⁴C–radiolabelled sulphur mustard (¹⁴C–SM). Animals were randomly assigned to either a control or a treatment group. In the latter, WoundStat™ was applied 30 s post exposure and left in situ for 1 h. Skin lesion progression and decontaminant efficacy were quantified over 6 h using a range of biophysical measurements. Skin, blood and organ samples were taken post mortem for histopathological assessment, ¹⁴C–SM distribution and toxicokinetic analyses. Application of SM to damaged skin without decontamination was rapidly followed by advanced signs of toxicity, including ulceration and decreased blood flow at the exposure site in all animals. WoundStat™ prevented ulceration and improved blood flow at the exposure site in all decontaminated animals (n = 6). Furthermore, significantly smaller quantities of ¹⁴C–SM were detected in the blood (45% reduction), and recovered from skin (70% reduction) and skin surface swabs (99% reduction) at 6 h post‐challenge. Overall, the distribution of ¹⁴C–SM in the internal organs was similar for both groups, with the greatest concentration in the kidneys, followed by the liver and small intestine. WoundStat™ significantly reduced the amount of ¹⁴C–SM recovered from the liver, a key organ for SM metabolism and detoxification. This study demonstrates that WoundStat™ is a suitable product for reducing the ingress and toxicity of a chemical warfare agent. Copyright © 2017 John Wiley & Sons, Ltd.     

Review of oximes in the antidotal treatment of poisoning by organophosphorus nerve agents

The cholinesterase-inhibiting organophosphorus compounds referred to as nerve agents (soman, sarin, tabun, GF agent, and VX) are particularly toxic and are considered to be among the most dangerous chemical warfare agents. Included in antidotal medical countermeasures are oximes to reactivate the inhibited cholinesterase. Much experimental work has been done to better understand the properties of the oxime antidotal candidates including the currently available pralidoxime and obidoxime, the H oximes HI-6 and Hl?-7, and methoxime. There is no single, broad-spectrum oxime suitablefor the antidotal treatment of poisoning with all organophosphorus agents. If more than one oxime is available, the choice depends primarily on the identity of the responsible organophosphorus compound. The H oximes appear to be very promising antidotes against nerve agents because they are able to protect experimental animals from toxic effects and improve survival of animals poisoned with supralethal doses. They appear more effective against nerve agent poisoning than the currently used oximes pralidoxime and obidoxime, especially in the case of soman poisoning. On the other hand, pralidoxime and especially obidoxime seem sufficiently effective to treat poisonings with organophosphorus insecticides that have relatively less toxicity than nerve agents.     

Quantitation of metabolites of the nerve agents sarin, soman, cyclohexylsarin, VX, and Russian VX in human urine using isotope-dilution gas chromatography-tandem mass spectrometry

Organophosphorus nerve agents are among the most toxic organic compounds known and continue to be a threat for both military and terrorist use. We have developed an isotope-dilution gas chromatography-tandem mass spectrometric (GC-MS-MS) method for quantitating the urinary metabolites of the organophosphorus nerve agents sarin (GB), soman (GD), VX, Russian VX (RVX), and cyclohexylsarin (GF). Urine samples were acidified, extracted into ether-acetonitrile, derivatized by methylation with diazomethane, and analyzed by GC-MS-MS. The limits of detection were less than 1 micro g/L for all analytes.     

Immunostimulant properties of polyoxidon on the model of acute poisoning with anticholinesterase chemicals in rats

Experiments on noninbred rats showed that, upon acute poisoning with toxic chemicals (sarin, VX agent; 1.0 LD50) and the treatment with atropine (10 mg/kg), the administration of polyoxidon in a daily dose of 100 mg/kg over 4 days partly reduces the degree of immune system suppression and the level of lipid peroxidation induced by toxic chemicals.     

Efficacy of a haemostatic matrix for the management of bleeding in patients undergoing liver resection: results from 237 cases

ABSTRACT

Background: The haemostatic matrix (FloSeal) is a topical agent that provides effective haemostasis in a range of surgical applications. We evaluated this sealant for intra-operative haemostatic effectiveness in an observational series of patients undergoing surgery for the resection of primary and metastatic liver tumours.

Methods: A haemostatic matrix was applied directly to areas of bleeding. The severity of bleeding before and after application was graded on a 5-point scale (0 = no bleeding, 1 = oozing, 2 = moderate blood flow, 3 = heavy blood flow, 4 = spurting blood). The time to complete haemostasis was also recorded.

Results: 105 women (age 61 ± 9 years) and 132 men (age 61 ± 12 years) were included in this study. One hundred and seventeen patients (49.36%) had pre-operative coagulopathy resulting from co-existent cirrhosis (67 Child-Pugh Class A; 50 Child-Pugh Class B). Prior to administration of a haemostatic matrix, 93 bleeding sites (24.8%) had a bleeding severity score of 2, 269 bleeding sites (71.7%) had a score of 3 and 13 bleeding sites (3.5%) had a score of 4. Following administration of the haemostatic matrix, bleeding stopped completely (score of 0) at 367 (97.9%) of the 375 sites and was reduced to a score of 1 at the remaining 8 sites (2.1%), of which only 2 were in patients with coagulopathy. The mean time to achieve haemostasis in the overall population was 2.9 ± 1?min; this was significantly increased in patients with coagulopathy versus non-coagulopathic patients (4 ± 1 vs. 2 ± 1?min, p < 0.001).

Conclusions: In this prospective, uncontrolled study of 237 consecutive patients undergoing major hepatic surgery to remove primary or metastatic tumours, application of a haemostatic matrix provided rapid and effective intra-operative control of mild to severe bleeding from the liver edge, even in patients with prolonged bleeding times resulting from cirrhosis. This preliminary evidence warrants a randomised, controlled clinical trial with a larger sample size.     

The reactivating and therapeutic efficacy of oximes to counteract Russian VX poisonings

Russian VX (O-isobutyl-S-(2-diethylaminoethyl)methylphosphonothioate) is the structural analogue of VX agent. It differs from VX agent (O-ethyl-S-(2-diisopropylaminoethyl) methylphosphonothioate) by two alkyl groups. The potency of currently available oximes (pralidoxime, obidoxime, HI-6) to reactivate Russian VX-inhibited acetylcholinesterase and to eliminate Russian VX-induced acute toxic effects was evaluated using in vivo methods. In vivo determined percentage of reactivation of Russian VX-inhibited blood and brain acetylcholinesterase in poisoned rats shows that HI-6 seems to be the most efficacious reactivator of Russian VX-inhibited acetylcholinesterase among currently used oximes in the peripheral compartment, whereas no difference between reactivating efficacy of all tested oximes was observed in the central compartment. The oxime HI-6 was also found to be the most efficacious oxime in the elimination of acute lethal toxic effects in Russian VX-poisoned mice among all studied oximes. Thus, the oxime HI-6 seems to be the most suitable oxime for the antidotal treatment of acute poisonings with Russian VX as in the case of VX, sarin, cyclosarin, and soman poisonings.     

An in vitro and in vivo evaluation of the efficacy of recombinant human liver prolidase as a catalytic bioscavenger of chemical warfare nerve agents

In this study, we determined the ability of recombinant human liver prolidase to hydrolyze nerve agents in vitro and its ability to afford protection in vivo in mice. Using adenovirus containing the human liver prolidase gene, the enzyme was over expressed by 200- to 300-fold in mouse liver and purified to homogeneity by affinity and gel filtration chromatography. The purified enzyme hydrolyzed sarin, cyclosarin and soman with varying rates of hydrolysis. The most efficient hydrolysis was with sarin, followed by soman and by cyclosarin {apparent k_cat/K_m [(1.9?±?0.3), (1.7?±?0.2), and (0.45?±?0.04)]?×?10^5?M^?1?min^?1, respectively}; VX and tabun were not hydrolyzed by the recombinant enzyme. The enzyme hydrolyzed P (+) isomers faster than the P (?) isomers. The ability of recombinant human liver prolidase to afford 24 hour survival against a cumulative dose of 2?×?LD₅₀ of each nerve agent was investigated in mice. Compared to mice injected with a control virus, mice injected with the prolidase expressing virus contained (29?±?7)-fold higher levels of the enzyme in their blood on day 5. Challenging these mice with two consecutive 1?×?LD₅₀ doses of sarin, cyclosarin, and soman resulted in the death of all animals within 5 to 8?min from nerve agent toxicity. In contrast, mice injected with the adenovirus expressing mouse butyrylcholinesterase, an enzyme which is known to afford protection in vivo, survived multiple 1?×?LD₅₀ challenges of these nerve agents and displayed no signs of toxicity. These results suggest that, while prolidase can hydrolyze certain G-type nerve agents in vitro, the enzyme does not offer 24 hour protection against a cumulative dose of 2?×?LD₅₀ of G-agents in mice in vivo.     

The prophylactic use of l-methyl, 2-hydroxyiminomethylpyridinium methanesulfonate (P2S) in the treatment of organophosphate poisoning.

Studies have been carried out to determine the effects of prophylactic treatment with P2S (1-methyl,2-hydroxyinimomethylpyridinium methanesulfonate) on the survival of animals poisoned by lethal doses of sarin, soman, tabun, or VX (O-ethyl S-diisopropylaminoethyl methylphosphonothiolate). The influence of such prophylaxis on the efficacy of therapy with atropine and P2S after poisoning by the same organophosphates has also been investigated. Following pretreatment with P2S there was a significant increase, compared with control animals, in the survival time of rabbits and guinea pigs poisoned by 2.3 LD50 of sarin and VX. With soman and tabun, the increase in the time of survival was slight, but consistent. In every case, the time taken for signs of poisoning to occur was unaffected by the pretreatment. P2S prophylaxis enhanced the effectiveness of therapy with atropine, and P2S given after poisoning with organophosphates had a similar effect, although the extent of the protection against soman poisoning was considerably less than that achieved against poisoning by sarin or VX.     

Comparison of skin decontamination strategies in the initial operational response following chemical exposures

In mass casualty incidents including hazardous chemical skin exposure, decontamination is the primary intervention to avoid systemic uptake of the toxic compound. The protocol needs to be both simple and efficient to enable a rapid response and avoid delay of patient management. In the present study, decontamination strategies included in the initial operational response were evaluated following human skin exposure in vitro to four different contaminants.Results demonstrated that the efficacy of selected decontamination procedures was highly dependent on the chemical contaminant used. Dry removal of the sulfur mustard simulant methyl salicylate prior to wet decontamination was found beneficial compared to wet decontamination alone. Rapidly initiated wet decontamination was more efficient compared to dry and wet removal of the industrial chemical 2-butoxyethanol and the nerve agent tabun. Following VX-exposure, all wet decontamination procedures resulted in increased agent penetration compared to the control.In conclusion, challenges in establishing simple and efficient decontamination procedures for a broad-spectrum of chemicals have been demonstrated. The impact of including a dry removal step during decontamination was evidently agent specific. Despite the variation in efficacy, immediately initiated dry removal may facilitate patient management until wet decontamination resources are available and to reduce the risk of secondary contamination.