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Environment International Nov 2008Sulphur Mustard, or "Mustard Gas" is in fact an oily liquid which was used as a chemical weapon primarily for its vesicant action which necessitates whole body... (Review)
Review
Sulphur Mustard, or "Mustard Gas" is in fact an oily liquid which was used as a chemical weapon primarily for its vesicant action which necessitates whole body protection. It is also now recognised as a carcinogenic agent upon chronic exposure. Soil contaminated with Sulphur Mustard continues to present both acute and chronic human health risks and risks to groundwater, surface water and the wider ecology at a number of sites globally and, in some cases, has done for many decades. This is at odds with the simple aqueous chemistry of the compound which would suggest that it should be short lived in the environment, especially in the presence of water. A number of studies have examined the possible factors for this longevity and, though the causes are generally assumed to be understood, the precise reasons have not yet been definitively determined and the evidence in support of the existing theories is at best circumstantial. At present, the prevailing view is that Sulphur Mustard is somehow protected by oligomeric or polymeric sulphonium species produced during incomplete hydrolysis reactions. The following review discusses the pertinent degradation mechanisms in the environment; hydrolysis and thermal degradation and the reasons put forward for the longevity of Sulphur Mustard in the literature. Other factors, such as the role of polymeric species in Sulphur Mustard droplets in modifying the mobility of the agent are also examined. Ultimately, without a thorough understanding of the abiotic fate of the Sulphur Mustard, uncertainties will remain in the application of risk assessment and remediation strategies to such sites, potentially compromising the validity or effectiveness of such actions.
Topics: Conservation of Natural Resources; Environmental Pollutants; Hydrolysis; Mustard Gas; Risk Assessment
PubMed: 18486211
DOI: 10.1016/j.envint.2008.03.012 -
Archives of Toxicology Nov 2022Chronic wounds, skin blisters, and ulcers are the result of skin exposure to the alkylating agent sulfur mustard (SM). One potential pathomechanism is senescence, which...
Chronic wounds, skin blisters, and ulcers are the result of skin exposure to the alkylating agent sulfur mustard (SM). One potential pathomechanism is senescence, which causes permanent growth arrest with a pro-inflammatory environment and may be associated with a chronic wound healing disorder. SM is known to induce chronic senescence in human mesenchymal stem cells which are subsequently unable to fulfill their regenerative function in the wound healing process. As dermal fibroblasts are crucial for cutaneous wound healing by being responsible for granulation tissue formation and synthesis of the extracellular matrix, SM exposure might also impair their function in a similar way. This study, therefore, investigated the SM sensitivity of primary human dermal fibroblasts (HDF) by determining the dose-response curve. Non-lethal concentrations LC (3 µM) to LC (65 µM) were used to examine the induction of senescence. HDF were exposed once to 3 µM, 13 µM, 24 µM, 40 µM or 65 μM SM, and were then cultured for 31 days. Changes in morphology as well as at the genetic and protein level were investigated. For the first time, HDF were shown to undergo senescence in a time- and concentration-dependent manner after SM exposure. They developed a characteristic senescence phenotype and expressed various senescence markers. Proinflammatory cytokines and chemokines were significantly altered in SM-exposed HDF as part of a senescence-associated secretory phenotype. The senescent fibroblasts can thus be considered a contributor to the SM-induced chronic wound healing disorder and might serve as a new therapeutic target in the future.
Topics: Alkylating Agents; Cellular Senescence; Cytokines; Fibroblasts; Humans; Mustard Gas; Skin
PubMed: 35906424
DOI: 10.1007/s00204-022-03346-7 -
Toxicology and Applied Pharmacology Apr 2005
Topics: Animals; Humans; Irritants; Mice; Models, Animal; Mustard Gas; Skin; Skin Absorption; Species Specificity
PubMed: 15781298
DOI: 10.1016/j.taap.2004.09.016 -
Combinatorial Chemistry & High... 2021Sulfur-(SM) and nitrogen (NM)-based mustards are the mutagenic incapacitating compounds which are widely used in vesicating the chemical warfare and cause toxicity in... (Review)
Review
BACKGROUND
Sulfur-(SM) and nitrogen (NM)-based mustards are the mutagenic incapacitating compounds which are widely used in vesicating the chemical warfare and cause toxicity in many organs, especially skin. SM, as a potent vesicating agent, contributes to the destruction of skin in dermis and epidermis layers. The progression of the lesion depends on the concentration of SM and the duration of exposure. Body responses start with pruritus, erythema, edema and xerosis, which lead to the accumulation of immune cells in the target sites and recruitment of mast cells and paracrine-mediated activity. Pro-inflammatory effectors are accumulated in the epidermis, hair follicles, and sebaceous glands resulting in the destruction of the basement membrane beneath the epidermis. There is still no satisfactory countermeasure against SM-induced lesions in clinical therapy, and the symptomatic or supportive treatments are routine management approaches.
OBJECTIVE
The current review highlights the recent progression of herbal medicines application in SM-induced injuries through the illustrative examples and also demonstrates their efficacies, properties and mechanism of actions as therapeutic agents.
CONCLUSION
Phytochemicals and herbal extracts with anti-bacterial, anti-inflammatory and antioxidant properties have been recently shown to hold therapeutic promise against the SM-induced cutaneous complications. The present review discusses the possible application of herbal medicines in the healing of SM-induced injuries.
Topics: Animals; Anti-Inflammatory Agents; Gas Scavengers; Herbal Medicine; Humans; Mustard Gas; Nitrogen; Phytochemicals; Plant Extracts; Plants, Medicinal; Skin; Sulfur; Wound Healing
PubMed: 32679016
DOI: 10.2174/1386207323666200717150414 -
Marine Environmental Research Aug 2009Microbiological studies were carried out on chemical weapon dump sites in the Baltic Sea. The effect of mustard gas hydrolysis products (MGHPs) on marine microbiota and...
Microbiological studies were carried out on chemical weapon dump sites in the Baltic Sea. The effect of mustard gas hydrolysis products (MGHPs) on marine microbiota and the ability of microorganisms to degrade MGHPs were studied. Many stations at the dump sites demonstrated reduced microbial diversity, and increased growth of species able to use mustard gas hydrolysis products as sole source of carbon. Significant amounts of MGHP-degrading bacteria were revealed in the near-bottom water. The MGHP-degrading microorganisms identified as Achromobacter sp., Pseudomonas sp., and Arthrobacter sp. were isolated. These microorganisms were capable of utilizing the major product of hydrolysis, thiodiglycol, as the sole source of carbon and energy. The bacteria were capable of metabolizing MGHPs at a low temperature. The metabolic pathway for thiodiglycol degradation was proposed. The results suggest the potential for MGHPs biodegradation by naturally occurring populations of near-bottom-water and sediment microorganisms.
Topics: Bacteria; Biomass; Biotransformation; Chemical Warfare Agents; Cloning, Organism; Environmental Monitoring; Geologic Sediments; Hydrolysis; Mustard Gas; Oceans and Seas; Seawater; Water Pollutants, Chemical
PubMed: 19481794
DOI: 10.1016/j.marenvres.2009.04.007 -
British Journal of Pharmacology and... Dec 1958The lethal effects of mustard gas, di(2-chloroethyl) sulphide, in the albino rat have been counteracted by Thiocit, a mixture of sodium thiosulphate and trisodium...
The lethal effects of mustard gas, di(2-chloroethyl) sulphide, in the albino rat have been counteracted by Thiocit, a mixture of sodium thiosulphate and trisodium citrate in the ratio 10:1, administered intraperitoneally in a dose of 2.75 g./kg. Thiocit afforded complete protection against greater than the median lethal dose of mustard gas whether given 10 min. before or 10 min. after mustard gas and raised the LD50 of mustard gas by approximately three times. The protection appeared whether the total dose of Thiocit was given in one injection or serially over 30 min. The effective doses of sodium thiosulphate and of Thiocit in rats were of the order of 3.0 g./kg. Sodium thiosulphate alone and Thiocit have been administered in single doses by slow infusion, by stomach tube and in drinking water. Both have shown activity by all routes of administration, but activity was greatest by intraperitoneal injection. The use of Thiocit in conjunction with mustard gas therapy is suggested.
Topics: Animals; Citrates; Injections, Intraperitoneal; Lethal Dose 50; Mustard Gas; Poisons; Rats; Sulfides; Thiosulfates
PubMed: 13618542
DOI: 10.1111/j.1476-5381.1958.tb00227.x -
Molecular Interventions Jun 2007
Topics: History, 19th Century; History, 20th Century; Mustard Gas; United States
PubMed: 17609517
DOI: 10.1124/mi.7.3.1 -
Analytical Chemistry Mar 2021Route determination of sulfur mustard was accomplished through comprehensive nontargeted screening of chemical attribution signatures. Sulfur mustard samples prepared...
Route determination of sulfur mustard was accomplished through comprehensive nontargeted screening of chemical attribution signatures. Sulfur mustard samples prepared via 11 different synthetic routes were analyzed using gas chromatography/high-resolution mass spectrometry. A large number of compounds were detected, and multivariate data analysis of the mass spectrometric results enabled the discovery of route-specific signature profiles. The performance of two supervised machine learning algorithms for retrospective synthetic route attribution, orthogonal partial least squares discriminant analysis (OPLS-DA) and random forest (RF), were compared using external test sets. Complete classification accuracy was achieved for test set samples (2/2 and 9/9) by using classification models to resolve the one-step routes starting from ethylene and the thiodiglycol chlorination methods used in the two-step routes. Retrospective determination of initial thiodiglycol synthesis methods in sulfur mustard samples, following chlorination, was more difficult. Nevertheless, the large number of markers detected using the nontargeted methodology enabled correct assignment of 5/9 test set samples using OPLS-DA and 8/9 using RF. RF was also used to construct an 11-class model with a total classification accuracy of 10/11. The developed methods were further evaluated by classifying sulfur mustard spiked into soil and textile matrix samples. Due to matrix effects and the low spiking level (0.05% w/w), route determination was more challenging in these cases. Nevertheless, acceptable classification performance was achieved during external test set validation: chlorination methods were correctly classified for 12/18 and 11/15 in spiked soil and textile samples, respectively.
Topics: Gas Chromatography-Mass Spectrometry; Mass Spectrometry; Mustard Gas; Retrospective Studies; Soil
PubMed: 33709707
DOI: 10.1021/acs.analchem.0c04555 -
The Journal of Pharmacology and... Jan 2024Sulfur mustard (SM) is an ominous chemical warfare agent. Eyes are extremely susceptible to SM toxicity; injuries include inflammation, fibrosis, neovascularization...
Sulfur mustard (SM) is an ominous chemical warfare agent. Eyes are extremely susceptible to SM toxicity; injuries include inflammation, fibrosis, neovascularization (NV), and vision impairment/blindness, depending on the exposure dosage. Effective countermeasures against ocular SM toxicity remain elusive and are warranted during conflicts/terrorist activities and accidental exposures. We previously determined that dexamethasone (DEX) effectively counters corneal nitrogen mustard toxicity and that the 2-hour postexposure therapeutic window is most beneficial. Here, the efficacy of two DEX dosing frequencies [i.e., every 8 or 12 hours (initiated, as previously established, 2 hours after exposure)] until 28 days after SM exposure was assessed. Furthermore, sustained effects of DEX treatments were observed up to day 56 after SM exposure. Corneal clinical assessments (thickness, opacity, ulceration, and NV) were performed at the day 14, 28, 42, and 56 post-SM exposure time points. Histopathological assessments of corneal injuries (corneal thickness, epithelial degradation, epithelial-stromal separation, inflammatory cell, and blood vessel counts) using H&E staining and molecular assessments (COX-2, MMP-9, VEGF, and SPARC expressions) were performed at days 28, 42, and 56 after SM exposure. Statistical significance was assessed using two-way ANOVA, with Holm-Sidak post hoc pairwise multiple comparisons; significance was established if < 0.05 (data represented as the mean ± S.E.M.). DEX administration every 8 hours was more potent than every 12 hours in reversing ocular SM injury, with the most pronounced effects observed at days 28 and 42 after SM exposure. These comprehensive results are novel and provide a comprehensive DEX treatment regimen (therapeutic-window and dosing-frequency) for counteracting SM-induced corneal injuries. SIGNIFICANCE STATEMENT: The study aims to establish a dexamethasone (DEX) treatment regimen by comparing the efficacy of DEX administration at 12 versus 8 hours initiated 2 hours after exposure. DEX administration every 8 hours was more effective in reversing sulfur mustard (SM)-induced corneal injuries. SM injury reversal during DEX administration (initial 28 days after exposure) and sustained [further 28 days after cessation of DEX administration (i.e., up to 56 days after exposure)] effects were assessed using clinical, pathophysiological, and molecular biomarkers.
Topics: Animals; Rabbits; Mustard Gas; Cornea; Chemical Warfare Agents; Corneal Injuries; Dexamethasone
PubMed: 37316330
DOI: 10.1124/jpet.123.001680 -
International Journal of Toxicology Mar 20112-Chloroethyl ethyl sulfide (CEES) or half-mustard gas, a sulfur mustard (HD) analog, is a genotoxic agent that causes oxidative stress and induces both apoptotic and...
2-Chloroethyl ethyl sulfide (CEES) or half-mustard gas, a sulfur mustard (HD) analog, is a genotoxic agent that causes oxidative stress and induces both apoptotic and necrotic cell death. Sodium pyruvate induced a necrosis-to-apoptosis shift in HaCaT cells exposed to CEES levels ≤ 1.5 mmol/L and lowered markers of DNA damage, oxidative stress, and inflammation. This study provides a rationale for the future development of multicomponent therapies for HD toxicity in the skin. We hypothesize that a combination of pyruvates with scavengers/antioxidants encapsulated in liposomes for optimal local delivery should be therapeutically beneficial against HD-induced skin injury. However, the latter suggestion should be verified in animal models exposed to HD.
Topics: Antioxidants; Apoptosis; Biomarkers; Cells, Cultured; DNA Damage; Drug Combinations; Humans; Inflammation; Keratinocytes; Liposomes; Mustard Gas; Necrosis; Oxidative Stress; Pyruvates; Skin
PubMed: 21300769
DOI: 10.1177/1091581810390824