Chemical Warfare Agent Degradation Products Research Articles

Acute toxicity of organoarsenic chemical warfare agents to Danio rerio embryos

During the 20th century, thousands of tons of munitions containing organoarsenic chemical warfare agents (CWAs) were dumped into oceans, seas and inland waters around the world. As a result, organoarsenic CWAs continue to leak from corroding munitions into sediments and their environmental concentrations are expected to peak over the next few decades. There remains, however, a lack of knowledge about their potential toxicity to aquatic vertebrates, such as fish. The aim of this study was to fill in this gap in research, by investigating the acute toxicity of organoarsenic CWAs on fish embryos, using the model species, Danio rerio. To estimate the acute toxicity thresholds of organoarsenic CWAs (Clark I, Adamsite, PDCA), a CWA-related compound (TPA), as well as four organoarsenic CWA degradation products (Clark I[ox], Adamsite[ox], PDCA[ox], TPA[ox]), standardized tests were performed following the OECD no. 236 Fish Embryo Acute Toxicity Test guidelines. Additionally, the detoxification response in D. rerio embryos was investigated by analysing the mRNA expression of five genes encoding antioxidant enzymes (CAT, SOD, GPx, GR and GST). During the 96 h of exposure, organoarsenic CWAs induced lethal effects in D. rerio embryos at very low concentrations (classified as 1st category pollutants according to GHS categorization), and were therefore deemed to be serious environmental hazards. Although TPA and the four CWA degradation products caused no acute toxicity even at their maximum solubility, the transcription of antioxidant-related genes was altered upon exposure to these compounds, indicating the need for further testing for chronic toxicity. Incorporating the results of this study into ecological risk assessments will provide a more accurate prediction of the environmental hazards posed by CWA-related organoarsenicals.

In-situ detoxification of schedule-I chemical warfare agents utilizing Zr(OH)4@W-ACF functional material for the development of next generation NBC protective gears

Chemical warfare agents (CWAs) have become a pivotal concern for the global community and spurred a wide spectrum of research for the development of new generation protective materials. Herein, a highly effective self-detoxifying filter consisting of in-situ immobilized Zirconium hydroxide [Zr(OH)4] over woven activated carbon fabric [Zr(OH)4@W-ACF] is presented for the removal of CWAs. It was prepared to harness the synergistic effect of high surface area of W-ACF, leads to high dispersion of CWAs and high phosphilicity and reactivity of [Zr(OH)4]. The synthesized materials were characterized by ATR-FTIR, EDX, SEM, TEM, XPS, TGA, and BET surface area analyzer. The kinetics of in-situ degradation of CWAs over Zr(OH)4@W-ACF were studied and found to be following the first-order reaction kinetics. The rate constant was found to be 0.244 min−1 and 2.31 × 10−2 min−1 for sarin and soman, respectively over Zr(OH)4@W-ACF. The potential practical applicability of this work was established by fabricating Zr(OH)4@W-ACF as reactive adsorbent layer for protective suit, and found to be meeting the specified criteria in terms of air permeability, tearing strength and nerve agent permeation as per TOP-08-2-501A:2013 and IS-17380:2020. The degradation products of CWAs were analyzed with NMR and GC–MS. The combined properties of dual functional textile with reactive material are expected to open up new exciting avenues in the field of CWAs protective clothing and thus find diverse application in defence and environmental sector.

Acute aquatic toxicity of arsenic-based chemical warfare agents to Daphnia magna

Sea dumping of chemical warfare (CW) took place worldwide during the 20th century. Submerged CW included metal bombs and casings that have been exposed for 50–100 years of corrosion and are now known to be leaking. Therefore, the arsenic-based chemical warfare agents (CWAs), pose a potential threat to the marine ecosystems. The aim of this research was to support a need for real-data measurements for accurate risk assessments and categorization of threats originating from submerged CWAs. This has been achieved by providing a broad insight into arsenic-based CWAs acute toxicity in aquatic ecosystems.Standard tests were performed to provide a solid foundation for acute aquatic toxicity threshold estimations of CWA: Lewisite, Adamsite, Clark I, phenyldichloroarsine (PDCA), CWA-related compounds: TPA, arsenic trichloride and four arsenic-based CWA degradation products.Despite their low solubility, during the 48 h exposure, all CWA caused highly negative effects on Daphnia magna. PDCA was very toxic with 48 h D. magna LC50 at 0.36 μg × L−1 and Lewisite with EC50 at 3.2 μg × L−1. Concentrations at which no immobilization effects were observed were slightly above the analytical Limits of Detection (LOD) and Quantification (LOQ). More water-soluble CWA degradation products showed no effects at concentrations up to 100 mg × L−1.

Acute aquatic toxicity of sulfur mustard and its degradation products to Daphnia magna

Sulphur mustard (HD) was the most widely produced chemical warfare agent (CWA) in the history of chemical warfare (CW). Simultaneously, the loads of HD account as by far the largest fraction of the sea-dumped CW. Nowadays its presence in the marine ecosystems recognized as a serious threat for marine users and maritime industries. Although, during over a decade of research much has been done to assess the environmental threats linked with underwater chemical munitions. There are, however, essential gaps in scientific knowledge including scarce information about the aquatic toxicity thresholds of HD and its degradation products.Standardized biotests were performed according to the Organisation for Economic Co-operation and Development (OECD) Test No. 202: Daphnia sp. Acute Immobilisation Test guidelines. Obtained results provide a solid foundation for comparison and categorisation of threats of HD and its degradation products. With the D. magna LC50 aquatic acute toxicity threshold at as low as 224 ± 12 μg × L−1, 1,2,5-trithiepane is very toxic, being one of the most toxic CWA degradation products that have been investigated up to date. It exhibits stronger effects than 1,4,5-oxadithiepane and diluted HD that turn out to be toxic. In total, the toxicity of 7 compounds has been estimated. Whenever possible, toxicity thresholds were compared with previously existing data originating from different biotests and mathematical modelling.

Versatile derivatization for GC-MS and LC-MS: alkylation with trialkyloxonium tetrafluoroborates for inorganic anions, chemical warfare agent degradation products, organic acids, and proteomic analysis.

Analytical chemists resort to derivatization for improving the detection performance of certain categories of analytes. Within this context, alkylation reactions are regarded as an important asset for many methods based on GC-MS and LC-MS. Trialkyloxonium tetrafluoroborates (R[Formula: see text][BF4]-) are powerful alkylating agents with ionic liquid properties: they are nonvolatile salts soluble in water which are easier and safer to handle with respect to common alkylating agents like diazomethane. R[Formula: see text][BF4]- can perform the alkylation in both organic and aqueous media at pH conditions ranging from acidic to alkaline. Recent analytical applications of trialkyloxonium derivatizations include the high-precision determination of inorganic anions in complex matrices, the qualitative confirmation of chemical warfare agent degradation products in soils, the profiling of carboxylic acids in urine, and the detection of protein post-translational modifications induced by carbon dioxide. The common denominator for all methods presented can be found in the simplicity of the alkylation protocol which, in most of the cases, requires a single step addition of the reagent directly to the sample. Graphical Abstract Alkylation with trialkyloxonium salts for GC-MS and LC-MS analysis.

Interrogating Proton Affinities of Organophosphonate Species Via Atmospheric Flow Tube Mass Spectrometry and Computational Methods.

Within trace vapor analysis in environmental monitoring, defense, and industry, atmospheric flow tube mass spectrometry (AFT-MS) can fill a role that incorporates non-contact vapor analysis with the selectivity and low detection limits of mass spectrometry. AFT-MS has been applied to quantitating certain explosives by selective clustering with nitrate and more recently applied to detecting tributyl phosphate and dimethyl methylphosphonate as protonated species. Developing AFT-MS methods for organophosphorus species is appealing, given that this class of compounds includes a range of pollutants, chemical warfare agent (CWA) simulants, and CWA degradation products. A key aspect of targeting organophosphorus analytes has included the use of dopant ion chemistry to form adducts that impart additional analytical selectivity. The assessment of potential dopant molecules suited to enhance detection of these compounds is hindered by few published ion thermochemical properties for organophosphorus species, such as proton affinity, which can be used for approximating proton-bound dimer bond strength. As a preliminary investigation for the progression of sensing methods involving AFT-MS, we have applied both the extended kinetic method and computational approaches to eight organophosphorus CWA simulants to determine their respective gas-phase proton affinities. Notable observed trends, supported by computational efforts, include an increase in proton affinity as the alkyl chain lengths on the phosphonates increased. Graphical Abstract .

Unexpected Reaction Pathways Leading to Thiodiglycol During the Degradation of Long-Chain Sulfur Mustards.

Degradation of long-chain sulfur mustards with various commercial decontaminants unexpectedly forms thiodiglycol (TDG) through unreported reaction pathways. Chemical warfare agents (CWAs) degradation products have to be unambiguously related to their reference compounds in order to fulfill international verification protocols. Thus, the formation of TDG using water-based decontaminants introduces an uncertainty in the origin of this chemical that has been systematically used to unambiguously demonstrate the presence of yperite in environmental and biomedical samples. Therefore, these novel and unprecedented degradation pathways will result either in modifications of the international verification protocols for forensic purposes or in the exclusion of TDG as an exclusive marker of yperite.

Tuning Mobility Separation Factors of Chemical Warfare Agent Degradation Products via Selective Ion-Neutral Clustering

Combining experimental data with computational modeling, we illustrate the capacity of selective gas-phase interactions using neutral gas vapors to yield an additional dimension of gas-phase ion mobility separation. Not only are the mobility shifts as a function of neutral gas vapor concentration reproducible, but also the selective alteration of mobility separation factors is closely linked to existing chemical functional groups. Such information may prove advantageous in elucidating chemical class and resolving interferences. Using a set of chemical warfare agent simulants with nominally the same reduced mobility values as a test case, we illustrate the ability of the drift-gas doping approach to achieve separation of these analytes. In nitrogen, protonated forms of dimethyl methyl phosphonate (DMMP) and methyl phosphonic acid (MPA) exhibit the reduced mobility values of 1.99 ± 0.01 cm2 V-1s-1 at 175 °C. However, when the counter current drift gas of the system is doped with 2-propanol at 20 μL/h, full baseline resolution of the two species is possible. By varying the concentration of the neutral modifier, the separation factor of the respective clusters can be adjusted. For the two species examined and at a 2-propanol flow rate of 160 μL/h, MPA demonstrated the greatest shift in mobility (1.58 cm2V-1s-1) compared the DMMP monomer (1.63 cm2V-1s-1). Meanwhile, the DMMP dimer experienced no change in mobility (1.45 cm2V-1s-1). The enhancement of separation factors appears to be brought about by the differential clustering of neutral modifiers onto different ions and can be explained by a model which considers the transient binding of a single 2-propanol molecule during mobility measurements. Furthermore, the application of the binding models not only provides a thermodynamic foundation for the results obtained but also creates a predictive tool toward a quantitative approach.

Novel analytical approaches to determination of chemical warfare agents and related compounds for verification of nonproliferation of chemical weapons

Abstract In this paper a summary of the author’s approaches for investigation of the mass spectral behavior of some chemical warfare agents (CWAs), their degradation products and metabolites, as well as the results of development of analytical methods for confirmation of nerve and blister agents application are presented. Hydrolysis and oxidation metabolites of nerve agents, sulfur mustard and lewisite were used as biomarkers of the exposure. Sensitive analytical methods have been developed for their detection, based mainly on tandem mass spectrometry coupled with liquid chromatography. Several techniques for fast screening of CWAs degradation products based on capillary electrophoresis were also proposed. Some of developed approaches were successfully applied in the frame of the proficiency testing system of the Organization for the Prohibition of Chemical Weapons.

Chemical Munitions Search & Assessment—An evaluation of the dumped munitions problem in the Baltic Sea

Chemical Munitions Search & Assessment (CHEMSEA) project has performed studies on chemical weapon (CW) detection, sediment pollution and spreading as well as biological effects of chemical warfare agents (CWAs) dumped in the Baltic Sea. Results suggest that munitions containing CWAs are more scattered on the seafloor than suspected, and previously undocumented dumpsite was discovered in Gdansk Deep. Pollution of sediments with CWA degradation products was local and close to the detected objects; however the pollution range was larger than predicted with theoretical models. Bottom currents observed in the dumpsites were strong enough for sediment re-suspension, and contributed to the transport of polluted sediments. Diversity and density of the faunal communities were poor at the dumping sites in comparison to the reference area, although the direct effects of CWA on benthos organisms were difficult to determine due to hypoxic or even anoxic conditions near the bottom. Equally, the low oxygen might have affected the biological effects assessed in cod and caged blue mussels. Nonetheless, both species showed significantly elevated molecular and cellular level responses at contaminated sites compared to reference sites.

Review of environmental exposure concentrations of chemical warfare agent residues and associated the fish community risk following the construction and completion of the Nord Stream gas pipeline between Russia and Germany

This paper compiles all the measured chemical warfare agent (CWA) concentrations found in relation to the Nord Stream pipeline work in Danish waters for the past 5 years. Sediment and biota sampling were performed along the pipeline route in four campaigns, prior to (in 2008 and 2010), during (in 2011) and after (in 2012) the construction work. No parent CWAs were detected in the sediments. Patchy residues of CWA degradation products of Adamsite, Clark I, phenyldichloroarsine, trichloroarsine and Lewisite II, were detected in a total of 29 of the 391 sediment samples collected and analyzed the past 5 years. The cumulative fish community risk quotient for the different locations, calculated as a sum of background and added risk, ranged between 0 and 0.017 suggesting a negligible acute CWA risk toward the fish community. The added risk from sediment disturbance in relation to construction of the pipelines represents less than 2% of the total risk in the areas with the highest calculated risk. The analyses of benthic infauna corroborate the finding of CWA related low risk across the years. There was no significant difference in CWA risk before (2008) and after the pipeline construction (2012).

Rapid screening of N-oxides of chemical warfare agents degradation products by ESI-tandem mass spectrometry

Rapid detection and identification of chemical warfare agents and related precursors/degradation products in various environmental matrices is of paramount importance for verification of standards set by the chemical weapons convention (CWC). Nitrogen mustards, N,N-dialkylaminoethyl-2-chlorides, N,N-dialkylaminoethanols, N-alkyldiethanolamines, and triethanolamine, which are listed CWC scheduled chemicals, are prone to undergo N-oxidation in environmental matrices or during decontamination process. Thus, screening of the oxidized products of these compounds is also an important task in the verification process because the presence of these products reveals alleged use of nitrogen mustards or precursors of VX compounds. The N-oxides of aminoethanols and aminoethylchlorides easily produce [M + H](+) ions under electrospray ionization conditions, and their collision-induced dissociation spectra include a specific neutral loss of 48 u (OH + CH2OH) and 66u (OH + CH2Cl), respectively. Based on this specific fragmentation, a rapid screening method was developed for screening of the N-oxides by applying neutral loss scan technique. The method was validated and the applicability of the method was demonstrated by analyzing positive and negative samples. The method was useful in the detection of N-oxides of aminoethanols and aminoethylchlorides in environmental matrices at trace levels (LOD, up to 500ppb), even in the presence of complex masking agents, without the use of time-consuming sample preparation methods and chromatographic steps. This method is advantageous for the off-site verification program and also for participation in official proficiency tests conducted by the Organization for the Prohibition of Chemical Weapons (OPCW), the Netherlands. The structure of N-oxides can be confirmed by the MS/MS experiments on the detected peaks. A liquid chromatography-mass spectrometry (LC-MS) method was developed for the separation of isomeric N-oxides of aminoethanols and aminoethylchlorides using a C18 Hilic column. Critical isomeric compounds can be confirmed by LC-MS/MS experiments, after detecting the N-oxides from the neutral loss scanning method.

Zirconia coated stir bar sorptive extraction combined with large volume sample stacking capillary electrophoresis-indirect ultraviolet detection for the determination of chemical warfare agent degradation products in water samples

In this study, a sensitive, selective and reliable analytical method by combining zirconia (ZrO2) coated stir bar sorptive extraction (SBSE) with large volume sample stacking capillary electrophoresis-indirect ultraviolet (LVSS-CE/indirect UV) was developed for the direct analysis of chemical warfare agent degradation products of alkyl alkylphosphonic acids (AAPAs) (including ethyl methylphosphonic acid (EMPA) and pinacolyl methylphosphonate (PMPA)) and methylphosphonic acid (MPA) in environmental waters. ZrO2 coated stir bar was prepared by adhering nanometer-sized ZrO2 particles onto the surface of stir bar with commercial PDMS sol as adhesion agent. Due to the high affinity of ZrO2 to the electronegative phosphonate group, ZrO2 coated stir bars could selectively extract the strongly polar AAPAs and MPA. After systematically optimizing the extraction conditions of ZrO2-SBSE, the analytical performance of ZrO2-SBSE-CE/indirect UV and ZrO2-SBSE-LVSS-CE/indirect UV was assessed. The limits of detection (LODs, at a signal-to-noise ratio of 3) obtained by ZrO2-SBSE-CE/indirect UV were 13.4–15.9μg/L for PMPA, EMPA and MPA. The relative standard deviations (RSDs, n=7, c=200μg/L) of the corrected peak area for the target analytes were in the range of 6.4–8.8%. Enhancement factors (EFs) in terms of LODs were found to be from 112- to 145-fold. By combining ZrO2 coating SBSE with LVSS as a dual preconcentration strategy, the EFs were magnified up to 1583-fold, and the LODs of ZrO2-SBSE-LVSS-CE/indirect UV were 1.4, 1.2 and 3.1μg/L for PMPA, EMPA, and MPA, respectively. The RSDs (n=7, c=20μg/L) were found to be in the range of 9.0–11.8%. The developed ZrO2-SBSE-LVSS-CE/indirect UV method has been successfully applied to the analysis of PMPA, EMPA, and MPA in different environmental water samples, and the recoveries for the spiked water samples were found to be in the range of 93.8–105.3%.

Evaluation of a chemical munition dumpsite in the Baltic Sea based on geophysical and chemical investigations

This paper discusses the results of geophysical and chemical investigations carried out in a chemical munition dumpsite in the southern Baltic Sea, east of the island of Bornholm. After WW2 over 32,000 tons of chemical war material was dumped here including shells and bombs as well as small drums and containers. The geophysical investigations combined very-high-resolution seismics and gradiometric measurements. The results indicate the presence of a large number of objects buried just below the seafloor. The size of the objects and their distribution, with a marked increase in density towards the center of the dumpsite, suggests that we are dealing with dumped war material. Sediment and near-bottom water samples, taken within the dumpsite and in the surrounding area, were analysed for the presence of various chemical warfare agents (CWA) including Adamsite, Clark, sulphur mustard, tabun, chlorobenzene and arsine oil. The results indicate a widespread contamination that reaches far beyond the dumpsite boundary. CWA degradation products were found in most of the sediment samples. The contamination was mostly related to arsenic containing compounds; only one sample indicated the presence of sulfur mustard. Although the correlation between detected objects and CWA concentrations is not always straightforward, the overall results suggest that a lot of the dumped war material is leaking and that over the years the contamination has reached the seafloor sediments.

Structural Characterization of Chemical Warfare Agent Degradation Products in Decontamination Solutions with Proton Band-Selective 1H−31P NMR Spectroscopy

Decontamination solutions, which are usually composed of strong alkaline chemicals, are used for efficient detoxification of chemical warfare agents (CWAs). The analysis of CWA degradation products directly in decontamination solutions is challenging due to the nature of the matrix. Furthermore, occasionally an unforeseen degradation pathway can result in degradation products which could be eluded to in standard analyses. Here, we present the results of the application of proton band-selective (1)H-(31)P NMR spectroscopy, i.e., band-selective 1D (1)H-(31)P heteronuclear single quantum coherence (HSQC) and band-selective 2D (1)H-(31)P HSQC-total correlation spectroscopy (TOCSY), for ester side chain characterization of organophosphorus nerve agent degradation products in decontamination solutions. The viability of the approach is demonstrated with a test mixture of typical degradation products of nerve agents sarin, soman, and VX. The proton band-selective (1)H-(31)P NMR spectroscopy is also applied in characterization of unusual degradation products of VX in GDS 2000 solution.

Enhancing determination of organophosphate species in high inorganic phosphate matrices: application to nerve agent degradation products

Developing a reliable and robust trace level method for organophosphates in the presence of relatively high inorganic phosphate is an area of interest for further method development. Since the advent of collision/reaction cell technology, inductively coupled plasma mass spectrometry (ICPMS) has been used with a variety of sample types for elemental phosphorus detection at m/z = 31. However, with many samples inorganic phosphate may be orders of magnitude higher than organophosphates, presenting a major interference to quantification. Therefore, removal of inorganic phosphate to levels low enough to minimize the interference would prove beneficial for more effective organophosphate analyses. In this study, applicable to most organophosphate containing samples, the illustration is to nerve agent degradation products as they might contaminate food and environmental systems after their initial formation. Calcium chloride was chosen as a coagulant mix and ammonium hydroxide was chosen to adjust the pH in order to remove inorganic phosphate at the sample preparation step. High performance liquid chromatography (HPLC) coupled with ICPMS was utilized for analysis. The results show that inorganic phosphate, at concentrations as high as 10 000 µg mL−1, can be sufficiently removed by precipitation with calcium at pH > 9 while the organophosphorus chemical warfare agent degradation products, CWADPs, remain intact. Applications to apple juice and cola drink indicate that this method is suitable for more complex matrices containing relatively high levels of inorganic phosphate.

Analysis of the degradation products of chemical warfare agents using a portable capillary electrophoresis instrument with various sample injection devices

In the present research, the performance of three sample injection devices in a portable capillary electrophoresis (CE) instrument was examined. These were the so-called cross-sampler, horizontal injection channel and vertical injection channel. All the three showed a good reproducibility of migration times (the relative standard deviation (RSD) was 4.3% in the case of the cross-sampler, 6.0% in the case of the horizontal injection channel and 1.7% in the case of the vertical channel). However, the reproducibility of peak areas was not sufficient. Hence, this study was mainly focused on qualitative analysis. The cross-sampler injection device was used in the portable CE instrument to analyse the composition of degradation products of chemical warfare agents (CWA). For the analysis of CWA degradation products simple procedures for the extraction of phosphonic acids from different surfaces, such as soil, concrete and granite blocks, tile floor, were developed.

Quantitative Analysis of Chemical Warfare Agent Degradation Products in Beverages by Liquid Chromatography Tandem Mass Spectrometry

Though chemical warfare agents (CWAs) have been banned by the Chemical Weapons Convention, the threat that such chemicals may be used, including their deliberate addition to food, remains. In such matrixes, CWAs may hydrolyze to phosphonic acids, which are good surrogate markers of CWA contamination. The method described here details the extraction of five CWA degradation products, including methylphosphonic acid (MPA), ethyl-MPA, isopropyl-MPA, cyclohexyl-MPA, and pinacolyl-MPA, from five different beverages by strata-X solid phase extraction cartridges. Samples were analyzed by liquid chromatography tandem mass spectrometry (LC/MS/MS) with multiple reaction monitoring. The limit of quantitation ranged from 0.05 to 0.5 ng on-column, and the limit of detection was >0.02 ng on-column. Beverages were fortified with the five phosphonic acids at 1 microg/mL and 0.25 microg/mL and quantitated using both an internally standardized method and matrix-matched standards. Reasonable recoveries (>50%) were achieved for ethyl, isopropyl, cyclohexyl, and pinacolyl-MPA for most matrixes.

Screening hydrolysis products of sulfur mustard agents by high-performance liquid chromatography with inductively coupled plasma mass spectrometry detection

Sulfur mustard (HD), bis(2-chloroethyl)sulfide, is one of a class of mustard agents which are chemical warfare agents. The main chemical warfare hydrolysis degradation products of sulfur mustards are: thiodiglycol, bis(2-hydroxyethylthio)methane, 1,2-bis(2-hydroxyethylthio)ethane, 1,3-bis(2-hydroxyethylthio)propane, and 1,4-bis(2-hydroxyethylthio)butane. The aim of this study is to identify these five hydrolysis degradation products utilizing reversed-phase high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry (ICP-MS) for element-specific sulfur detection using a collision/reaction cell and electrospray ionization mass spectrometry to confirm the identification. To date, this is the first study utilizing ICP-MS with (32)S element-specific detection for the analysis of vesicant chemical warfare agent degradation products.

Cytotoxicity of arsenic-containing chemical warfare agent degradation products with metallomic approaches for metabolite analysis

The arsenic metallome in African Green Monkey kidney cells is probed by measuring cytotoxicity, cellular arsenic uptake and speciation studies on arsenic-containing chemical warfare agent degradation products (CWDPs) during cell uptake. Inorganic arsenic compounds and methylated species also were studied during cell uptake as a means of providing cytotoxicity information relative to the CWDPs. The degradation products used were phenylarsine oxide (PAO), phenylarsonic acid (PAA), diphenylarsinic acid (DPAA), triphenylarsine (TPA) and triphenylarsine oxide (TPAO). These are the warfare agent’s primary degradation products. The parent warfare agents (red agents) are diphenylarsine chloride (DA or referred to as Clark I) and diphenylarsine cyanide (DC or Clark II), sternutator agents, sneezing gases able to cause bronchial irritation. Cytotoxicity levels and cellular uptake were compared to those of inorganic species: sodium arsenite, NaAsO2 [As(III)], sodium arsenateNa2HAsO4 [As(V)] and methylated arsenicals such as dimethylarsinic acid (DMA) and methylarsonic acid (MMA). The arsenic uptake was demonstrated in an African Green Monkey kidney cell line, CV-1. Quantification of lactate dehydrogenase activityreleased from damaged/dying cells was then measured via an LDH assay. The purpose of this study is to initially investigate toxicity to cells when exposed to different arsenic containing compounds over different concentrations and time ranges from 3 h to 24 h. Furthermore, exposed cells were then analyzed for different arsenic species by high performance liquid chromatography (HPLC) with inductively coupled plasma mass spectrometry to isolate and speciate arsenic fractions followed by nanoLC electrospray ionization mass spectrometry to analyze the molecular level changes of the arsenic based degradation products in the kidney cells. Metabolic changes to the arsenic species were found, and interestingly, at the lowest uptake levels, cytotoxicities were generally higher for the chemical warfare agent degradation products than the inorganic arsenic species.