Chemical Warfare Agents Sarin Research Articles

Theoretical study of surface-enhanced Raman spectroscopy of dimethyl methylphosphonate

In this study, the surface-enhanced Raman spectroscopy spectra of dimethyl methyl phosphonate, which serves as a surrogate for the chemical warfare agent sarin, were modeled using density functional theory calculations. In addition, the fundamental mechanisms underlying the enhancement of surface-enhanced Raman spectroscopy are investigated. A comprehensive examination was conducted of the adsorption behavior and Surface-Enhanced Raman Spectroscopy enhancement effects resulting from the interaction between dimethyl methylphosphonate and silver clusters. Moreover, a comparison was made between the findings of the present study and the results of previous experiments in order to ascertain the optimal positions for the adsorption of silver clusters on dimethyl methylphosphonate molecules. In this article, the kinetics of the interaction between dimethyl methylphosphonate and silver clusters were theoretically explored through six different adsorption configurations. It was found that the configuration involving the dimethyl methylphosphonate structure and silver clusters containing three silver atoms exhibited the highest stability. By integrating Raman spectroscopic data with our theoretical insights, the vibrational modes, Raman spectra, and surface-enhanced Raman spectra of dimethyl methylphosphonate molecules were systematically correlated using Gaussian 09 and GaussView 5.0.8 software for detailed image-based analysis.

Reliable Detection of Chemical Warfare Agents Using High Kinetic Energy Ion Mobility Spectrometry.

High Kinetic Energy Ion Mobility Spectrometers (HiKE-IMS) ionize and separate ions at reduced pressures of 10-40 mbar and over a wide range of reduced electric field strengths E/N of up to 120 Td. Their reduced operating pressure is distinct from that of conventional drift tube ion mobility spectrometers that operate at ambient pressure for trace compound detection. High E/N can lead to a field-induced fragmentation pattern that provides more specific structural information about the analytes. In addition, operation at high E/N values adds the field dependence of ion mobility as an additional separation dimension to low-field ion mobility, making interfering compounds less likely to cause a false positive alarm. In this work, we study the chemical warfare agents tabun (GA), sarin (GB), soman (GD), cyclosarin (GF) and sulfur mustard (HD) in a HiKE-IMS at variable E/N in both the reaction and the drift region. The results show that varying E/N can lead to specific fragmentation patterns at high E/N values combined with molecular signals at low E/N. Compared to the operation at a single E/N value in the drift region, the variation of E/N in the drift region also provides the analyte-specific field dependence of ion mobility as additional information. The accumulated data establish a unique fingerprint for each analyte that allows for reliable detection of chemical warfare agents even in the presence of interfering compounds with similar low-field ion mobilities, thus reducing false positives.

SIMULATING VICTIM HEALTH STATE EVOLUTION FROM PHYSICAL AND CHEMICAL INJURIES IN MASS CASUALTY INCIDENTS

The field of discrete-event simulation for medical disaster management is relatively new. In such simulations, human victims are generated using pre-determined transitions from one health state to the next, based on a set of triggers that correspond to treatment or the clinical progression of untreated injuries or diseases. However, this approach does not account for subtle differences in clinical progression. We propose a parameter-based model to characterize the evolution of symptoms at first for physical and nerve agent chemical injuries. We used a Gompertz function to predict the time of death in trauma based on forensic data. Then we separately considered the effects of the chemical warfare agent sarin (GB) being the origin of the chemical injuries for the purpose of modelling a GB attack in a metro station. We emphasize that our approach can be extended to other CBRN threats pending knowledge of clinical progressions available in the literature for the purpose of casualty estimations. The intent is to provide an estimate of time to death without any treatment and overlay this model with a treatment model, improving the evolution of the health state. A modification for non-life-threatening injuries is included without losing generality. Improvement functions modelling medical treatment are proposed. We argue that the availability of injury scores vs mortality can greatly enhance the validity of the model.

The Application of Microfibrous Entrapped Activated Carbon Composite Material for the Sarin Simulant Dimethyl Methylphosphonate Adsorption.

Granular activated carbon (GAC) has proven to be an effective adsorbent for removing the chemical warfare agent sarin (GB) and simulants like Dimethyl methylphosphonate (DMMP). However, it comes with certain limitations, including inadequate contact efficiency, notable mass transfer resistance, and lower bed utilization efficiency. This study synthesized steel fiber-entrapped activated carbon composites (SFEACs), which exhibited a maximum adsorption capacity of 285.3 mg/g at 303 K. Compared with the packed bed (PB) filled with GAC, while the adsorption capacity of SFEACS decreased, there was a substantial increase in the adsorption mass transfer rate. These SFEACs were combined with GAC to create a structural fixed bed (SFB), which demonstrated excellent performance in DMMP removal. Under identical experimental conditions, the DMMP breakthrough curve of SFB exhibited a steeper profile compared to the packed bed (PB) filled with GAC at the same bed height, and the breakthrough time against DMMP vapor could be extended by 13.8%. Furthermore, the adsorption rate constant of the Yoon-Nelson model increased by more than 17.6%, and the unused bed length, according to the Wheeler-Jonas model, decreased by more than 14%.

The preservation of sarin and O,O'-diisopropyl fluorophosphate inside coordination cage hosts.

The host-guest chemistry of O,O'-diisopropyl fluorophosphate (DFP), a phosphonofluoridate G-series chemical warfare agent simulant, was investigated in the presence of a number of octanuclear cubic coordination cage hosts. The aim was to demonstrate cage-catalysed hydrolysis of DFP at near neutral pH: however, two octanuclear coordination cages, HPEG (containing water-solubilising PEG groups) and HW (containing water-solubilising hydroxymethyl groups), were actually found to increase the lifetime of DFP in aqueous buffer solution (pH 8.7). Crystallographic analysis of DFP with a structurally related host cage revealed that DFP binds to windows in the cage surface, not in the internal cavity. The phosphorus-fluorine bond is directed into the cavity rather than towards the external environment, with the cage/DFP association protecting DFP from hydrolysis. Initial studies with the chemical warfare agent (CWA) sarin (GB) with HPEG cage in a buffered solution also showed a drastically reduced rate of hydrolysis for sarin when bound in the host cage. The ability of these cages to inhibit hydrolysis of these P-F bond containing organophosphorus guests, by encapsulation, may have applications in forensic sample preservation and analysis.

High reactivity of mesoporous CeO2 to dissociate chemical warfare agent sarin

Spectroscopic surface characterization under exposure of sarin gas (also known as GB) as well as DFT modeling reveals the high reactivity of mesoporous ceria (CeO2) towards sarin degradation.

Au@ZrO2 core‐shell nanoparticles as a surface‐enhanced Raman scattering substrate for organophosphorus compounds detection

AbstractOrganophosphorus (OPs) compounds have received enormous attention due to high neurotoxicity. However, the complex detection environment makes it very difficult to detect the OPs compounds at extremely low‐concentration. Therefore, it is vital to develop a high sensitive analytical method for the detection of low‐concentration OPs compounds at complex environment. Here, we proposed a novel surface‐enhanced Raman scattering (SERS) substrate based on the core‐shell structure Au@ZrO2 for the detection of extremely low‐concentration OPs compounds. By using above SERS substrate, we tested different kinds of OPs compounds and obtained excellent detection results. The detection limit of methyl parathion and triazophos can reach 0.01 mg/kg. Meanwhile, under the actual system (orange peel), the detection limit of the methyl parathion and triazophos also can reach 0.5 and 0.1 mg/kg, respectively. In addition, the above substrate is also very effective for the detection of dimethyl methylphosphonate (DMMP), a simulant for the chemical warfare agent (sarin), and the detection limit can reach 100 mg/kg. Besides, we also verified the reproducibility and stability of Au@ZrO2, which showed excellent properties. The relative standard deviation (RSD) of the SERS signal intensity for 20 tests was 6.38% and the enhancement ability of Au@ZrO2 can remain stable within 30 days. These results show that the proposed Au@ZrO2 SERS substrate has great potential in the detection of OPs compounds at extremely low‐concentration in the complex detection environment.

Decomposition for Chemical Warfare Agent Sarin: Comparation Between Plate-to-Plate and Plate-to-Pin Dielectric Barrier Discharge

The degradation of chemical warfare agent (CWA) sarin using plate-to-plate and plate-to-pin electrode structure dielectric barrier discharges (DBDs) was studied in this work. The discharge characteristics, optical emission, decomposition efficiency, and decomposition products in the above apparatus were well investigated. With initial pure sarin of <inline-formula> <tex-math notation="LaTeX">$20 ~\mu \text{L}$ </tex-math></inline-formula>, the decomposition amount per unit time and decomposition efficiency were obtained to be <inline-formula> <tex-math notation="LaTeX">$14.68 \times 10^{-3}$ </tex-math></inline-formula> mg/s and <inline-formula> <tex-math notation="LaTeX">$0.25 ~\mu \text{g}$ </tex-math></inline-formula>/J, for plate-to-plate DBD, and <inline-formula> <tex-math notation="LaTeX">$9.16 \times 10^{-3}$ </tex-math></inline-formula> mg/s and <inline-formula> <tex-math notation="LaTeX">$0.167 ~\mu \text{g}$ </tex-math></inline-formula>/J, for plate-to-pin DBD, respectively. The decomposition products containing isopropyl methylphosphoric acid (IMPA), methylphosphoric acid (MPA), fluoro(methyl)phosphinic acid (MPFA), di-isopropyl methane phosphate (DIMP), and phosphoric acid (PA) were observed in both DBD devices, with MPA and PA as the final products. The production level of PA was highest among all the products in plate-to-plate DBD. However, in plate-to-pin DBD, the concentration of PA and MPA were at the same level. The different decomposition efficiency between two DBD devices were mainly ascribed to the different input energy and their configuration. Our results confirmed that plate-to-plate DBD was a high-efficiency decomposition technology for sarin decomposition.

A prototype portable instrument employing micro-preconcentrator and FBAR sensor for the detection of chemical warfare agents

The presence of chemical warfare agents (CWAs) in the environment is a serious threat to human safety, but there are many problems with the currently available detection methods for CWAs. For example, gas chromatography–mass spectrometry cannot be used for in-field detection owing to the rather large size of the equipment required, while commercial sensors have the disadvantages of low sensitivity and poor selectivity. Here, we develop a portable gas sensing instrument for CWA detection that consists of a MEMS-fabricated micro-preconcentrator (μPC) and a film bulk acoustic resonator (FBAR) gas sensor. The μPC is coated with a nanoporous metal–organic framework material to enrich the target, while the FBAR provides rapid detection without the need for extra carrier gas. Dimethyl methylphosphonate (DMMP), a simulant of the chemical warfare agent sarin, is used to test the performance of the instrument. Experimental results show that the μPC provides effective sample pretreatment, while the FBAR gas sensor has good sensitivity to DMMP vapor. The combination of μPC and FBAR in one instrument gives full play to their respective advantages, reducing the limit of detection of the analyte. Moreover, both the μPC and the FBAR are fabricated using a CMOS-compatible approach, and the prototype instrument is compact in size with high portability and thus has potential for application to in-field detection of CWAs.

Ultrafast-response, highly-sensitive and recyclable colorimetric/fluorometric dual-channel chemical warfare agent probes

In this paper, two donor (D)-acceptor (A) type of small organic fluorescent molecules (T1 and T2) based on terpyridine group are synthesized, characterized and used as colorimetric/fluorometric dual-channel probes towards diethylchlorophosphate (DCP, the mimic of chemical warfare agent sarin) not only in solution but also in gas phase featuring instantaneous responses, excellent recyclability, high selectivity and sensitivity. Interestingly though the discriminated units of both chemosensors are terpyridine, their fluorescent responded signals are different, which is due to the different electron-donating substituents of T1 and T2 caused the different responded mechanism to DCP. And the possible sensing mechanism was proved by using nuclear magnetic resonance (1H NMR, 31P NMR) spectra and natural transition orbitals calculations. Furthermore, facile testing filter paper-constructed strips with the visualization of colorimetric/fluorometric dual-channel responses based on T1 and T2 have been fabricated for real-time, on-site high selective and sensitive, recyclable monitor of DCP vapor.

Development of a High-Efficiency Decomposition Technology for Volatile Chemical Warfare Agent Sarin Using Dielectric Barrier Discharge

High-efficiency decomposition technology for volatile chemical warfare agent sarin was developed using a dielectric-barrier discharge (DBD). The power consumptions of the developed device for which the gap lengths of the plasma-generation sites were 1.0–2.0 mm, were found to be 22–27 W, respectively. The DBD driven sarin-decomposition amount per unit time and the decomposition efficiency in the optimized condition were obtained to be 2.05 × 10−3 mg/s and 1.38 × 10−4 mg/W, respectively, measured by ion mobility spectrometer. Sarin-decomposition products were investigated using a gas chromatography–mass spectrometry with tert-butyldimethylsilylation derivatization, indicating that isopropyl methylphosphoric acid (IMPA), methylphosphoric acid (MPA), and phosphoric acid (PA) were generated during sarin decomposition by DBD. The decomposition efficiency at 37 W decreased by 41% molar concentration compared with that at 15 W, but the production levels of IMPA, MPA and PA were changed from 10.0%, 41.5% and 3.9% to 7.2%, 21.3% and 6.4%, respectively.

Neurosteroid and benzodiazepine combination therapy reduces status epilepticus and long-term effects of whole-body sarin exposure in rats.

ObjectiveOur objective was to evaluate the protective efficacy of the neurosteroid pregnanolone (3α‐hydroxy‐5β pregnan‐20‐one), a GABAA receptor‐positive allosteric modulator, as an adjunct to benzodiazepine therapy against the chemical warfare nerve agent (CWNA) sarin (GB), using whole‐body exposure, an operationally relevant route of exposure to volatile GB.MethodsRats implanted with telemetry transmitters for the continuous measurement of cortical electroencephalographic (EEG) activity were exposed for 60 minutes to 3.0 LCt50 of GB via whole‐body exposure. At the onset of toxic signs, rats were administered an intramuscular injection of atropine sulfate (2 mg/kg) and the oxime HI‐6 (93.6 mg/kg) to increase survival rate and, 30 minutes after seizure onset, treated subcutaneously with diazepam (10 mg/kg) and intravenously with pregnanolone (4 mg/kg) or vehicle. Animals were evaluated for GB‐induced status epilepticus (SE), spontaneous recurrent seizures (SRS), impairment in spatial memory acquisition, and brain pathology, and treatment groups were compared.ResultsDelayed dual therapy with pregnanolone and diazepam reduced time in SE in GB‐exposed rats compared to those treated with delayed diazepam monotherapy. The combination therapy of pregnanolone with diazepam also prevented impairment in the Morris water maze and reduced the neuronal loss and neuronal degeneration, evaluated at one and three months after exposure.SignificanceNeurosteroid administration as an adjunct to benzodiazepine therapy offers an effective means to treat benzodiazepine‐refractory SE, such as occurs following delayed treatment of GB exposure. This study is the first to present data on the efficacy of delayed pregnanolone and diazepam dual therapy in reducing seizure activity, performance deficits and brain pathology following an operationally relevant route of exposure to GB and supports the use of a neurosteroid as an adjunct to standard anticonvulsant therapy for the treatment of CWNA‐induced SE.

Computational Screening of Roles of Defects and Metal Substitution on Reactivity of Different Single- vs Double-Node Metal–Organic Frameworks for Sarin Decomposition

Understanding how different factors affect the electronic properties of metal–organic frameworks (MOFs) is critical to understanding their potential for catalysis and to serve as catalyst supports. In this work, periodic dispersion-corrected quantum mechanical calculations are performed to assess the catalytic activity of different Zr6 vs Zr12 MOFs for the heterogeneous catalytic hydrolysis of the chemical warfare agent sarin. Using a comprehensive series of extended periodic models capable of capturing long-range sarin/water/framework interactions in both Zr6 and Zr12 MOFs, the effects of numbers and morphologies of defective sites, as well as ZrIV substitution with heavier CeIV, are thoroughly investigated. Our calculations show that hydrogen bonds involving both metal-oxide nodes and organic linkers can play important roles in the catalysis. Insights derived from this work should inform the design and realization of more effective and robust next-generation MOF-based heterogeneous catalysts.

Radiosynthesis of O-(1-[18 F]fluoropropan-2-yl)-O-(4-nitrophenyl)methylphosphonate: A novel PET tracer surrogate of sarin.

O-(1-Fluoropropan-2-yl)-O-(4-nitrophenyl) methylphosphonate is a reactive organophosphate ester (OP) developed as a surrogate of the chemical warfare agent sarin that forms a similar covalent adduct at the active site serine of acetylcholinesterase. The radiolabeled O-(1-[18 F]fluoropropan-2-yl)-O-(4-nitrophenyl) methylphosphonate ([18 F] fluorosarin surrogate) has not been previously prepared. In this paper, we report the first radiosynthesis of this tracer from the reaction of bis-(4-nitrophenyl) methylphosphonate with 1-[18 F]fluoro-2-propanol in the presence of DBU. The 1-[18 F]fluoro-2-propanol was prepared by reaction of propylene sulfite with Kryptofix 2.2.2 and [18 F] fluoride ion. The desired tracer O-(1-[18 F]fluoropropan-2-yl)-O-(4-nitrophenyl) methylphosphonate was obtained in a >98% radiochemical purity with a 2.4%±0.6% yield (n=5, 65minutes from start of synthesis) based on starting [18 F] fluoride ion and a molar activity of 49.9GBq/μmol (1.349±0.329Ci/μmol, n=3). This new facile radiosynthesis routinely affords sufficient quantities of [18 F] fluorosarin surrogate in high radiochemical purity, which will further enable the tracer development as a novel radiolabeled OP acetylcholinesterase inhibitor for assessment of OP modes of action with PET imaging in vivo.

Spectroscopic and inclusion properties of G-series chemical warfare agents and their simulants: a DFT study

A computational protocol to predict the infrared spectra of chemical warfare agents (CWAs) tabun (GA), sarin (GB), soman (GD) and cyclosarin (GF) has been developed. Sarin was used to benchmark the method through gas phase simulations. DFT calculations using the EDF2 functional and diffuse 6-311++G** basis set was found to give the closest match to experimental infrared spectra. Using the same functional the 6-31G (2df, 2p) basis set was found to be superior when hydrated sarin was modelled. GA, GB, GD and GF, together with 11 commonly used simulants, were modelled in the gas and hydrated states. Complexes of GB and a number of CWA mimics with α-cyclodextrin were modelled to give insight into their different modes of inclusion.

The Cu- and Zn-complex-catalyzed methanolysis of the chemical warfare nerve agents soman, sarin, and VX

The catalytic methanolysis of the chemical warfare nerve agents soman, sarin, and VX was investigated by using Cu or Zn complexes. Although VX withstood decontamination, the decomposition yield being around 96%, the soman and sarin deposited on different surfaces were almost fully destroyed under ambient conditions. The catalytic tests performed on a wide range of contaminated surfaces confirm the activity of the investigated catalytic systems, these complexes being suitable, from an economical point of view, for use in the formulation of a possible decomposition kit with military or civilian applicability. La méthanolyse catalytique des agents neurotoxiques de guerre chimique soman, sarin et VX a été étudiée en utilisant des complexes du Cu ou du Zn. Bien que VX résiste à la décontamination, le rendement de décomposition étant d'environ 96%, le soman et le sarin déposés sur différentes surfaces ont été presque entièrement détruits dans les conditions ambiantes. Les essais catalytiques effectués sur une large gamme de surfaces contaminées confirment l'activité des systèmes catalytiques étudiés, ces complexes étant appropriés d'un point de vue économique pour être utilisés dans la formulation d'un éventuel kit de décomposition militaire ou civil.

Engineering Bacteria to Catabolize the Carbonaceous Component of Sarin: Teaching E. coli to Eat Isopropanol.

We report an engineered strain of Escherichia coli that catabolizes the carbonaceous component of the extremely toxic chemical warfare agent sarin. Enzymatic decomposition of sarin generates isopropanol waste that, with this engineered strain, is then transformed into acetyl-CoA by enzymatic conversion with a key reaction performed by the acetone carboxylase complex (ACX). We engineered the heterologous expression of the ACX complex from Xanthobacter autotrophicus PY2 to match the naturally occurring subunit stoichiometry and purified the recombinant complex from E. coli for biochemical analysis. Incorporating this ACX complex and enzymes from diverse organisms, we introduced an isopropanol degradation pathway in E. coli, optimized induction conditions, and decoupled enzyme expression to probe pathway bottlenecks. Our engineered E. coli consumed 65% of isopropanol compared to no-cell controls and was able to grow on isopropanol as a sole carbon source. In the process, reconstitution of this large ACX complex (370 kDa) in a system naïve to its structural and mechanistic requirements allowed us to study this otherwise cryptic enzyme in more detail than would have been possible in the less genetically tractable native Xanthobacter system.

Oximes in organophosphate poisoning: 60 years of hope and despair

The high number of annual fatalities following suicidal poisoning by organophosphorus (OP) pesticides and the recent homicidal use of the chemical warfare nerve agent sarin against civilian population in Syria underlines the continuous threat by these highly toxic agents. The need for an effective treatment of OP poisoning resulted in the implementation of a combination therapy with the muscarinic receptor antagonist atropine and an oxime for the reactivation of OP-inhibited acetylcholinesterase (AChE). Since the invention of the first clinically used oxime pralidoxime (2-PAM) in the 1950s ongoing research attempted to identify more effective oximes. In fact, several thousand oximes were synthesized in the past six decades. These include charged and non-charged compounds, mono- and bispyridinium oximes, asymmetric oximes, oximes with different substitutes and more recently non-oxime reactivators. Multiple in vitro and in vivo studies investigated the potential of oximes to reactivate OP-inhibited AChE and to reverse OP-induced cholinergic signs. Depending on the experimental model, the investigated species and the tested OP largely variable results were obtained by different laboratories. These findings and the inconsistent effectiveness of oximes in the treatment of OP-pesticide poisoned patients led to a continuous discussion on the value of oximes. In order to provide a forward-looking evaluation of the significance of oximes in OP poisoning multiple aspects, including intrinsic toxicity, in vitro reactivation potency, efficacy and pharmacokinetics, as well as the impact of the causative OP have to be considered. The different influencing factors in order to define the benefit and limitations of oximes in OP poisoning will be discussed.

Selective Surface Acoustic Wave-Based Organophosphorus Sensor Employing a Host-Guest Self-Assembly Monolayer of β-Cyclodextrin Derivative.

Self-assembly and molecular imprinting technologies are very attractive technologies for the development of artificial recognition systems and provide chemical recognition based on need and not happenstance. In this paper, we employed a β-cyclodextrin derivative surface acoustic wave (SAW) chemical sensor for detecting the chemical warfare agents (CWAs) sarin (O-Isoprophyl methylphosphonofluoridate, GB). Using sarin acid (isoprophyl hydrogen methylphosphonate) as an imprinting template, mono[6-deoxy-6-[(mercaptodecamethylene)thio]]-β-cyclodextrin was prepared by self-assembled method on one of the SAW oscillators. After templates’ removal, a sensitive and selective molecular imprinting (MIP) monolayer for GB was prepared. Electrochemical impedance spectroscopy and atomic force microscope (AFM) were used to characterize this film. Comparing the detection results to GB by MIP film and non-MIP film, the molecularly imprinting effect was also proved. The resulting SAW sensor could detect sarin as low as 0.10 mg/m3 at room temperature and the frequency shift was about 300 Hz. The response frequency increased linearly with increasing sarin concentration in the range of 0.7 mg/m3~3.0 mg/m3. When sarin was detected under different temperatures, the SAW sensor exhibited outstanding sensitivity and reliability.

Beneficial effects of a ketamine/atropine combination in soman-poisoned rats under a neutral thermal environment

Exposure to organophosphorus (OP) compounds, such as pesticides and the chemical warfare agents (soman and sarin), respectively represents a major health problem and a threat for civilian and military communities. OP poisoning may induce seizures, status epilepticus and even brain lesions if untreated. We recently proved that a combination of atropine sulfate and ketamine, a glutamatergic antagonist, was effective as an anticonvulsant and neuroprotectant in mice and guinea-pigs exposed to soman. Since OP exposure may also occur in conditions of heat strain due to climate, wearing of protective gears or physical exercise, we previously demonstrated that ketamine/atropine association may be used in a hot environment without detrimental effects. In the present study, we assess soman toxicity and evaluate the effects of the ketamine/atropine combination on soman toxicity in a warm thermoneutral environment. Male Wistar rats, exposed to 31°C (easily reached under protective equipments), were intoxicated by soman and treated with an anesthetic dose of ketamine combined with atropine sulfate. Body core temperature and spontaneous locomotor activity were continuously monitored using telemetry. At the end of the warm exposure, blood chemistry and brain mRNA expression of some specific genes were measured. In soman-intoxicated animals, metabolic and genic modifications were related to convulsions rather than to soman intoxication by itself. In the warm environment, ketamine/atropine combination did not produce any side-effect on the assessed variables. Furthermore, the ketamine/atropine combination exhibited beneficial therapeutic effects on soman-intoxicated rats such as a limitation of convulsion-induced hyperthermia and of the increase in some blood chemistry markers.