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Journal of Analytical Toxicology 2008Sulfur mustard (HD) is an alkylating agent that reacts rapidly with macromolecular targets resulting in the formation of stable adducts providing depots for markers of...
Sulfur mustard (HD) is an alkylating agent that reacts rapidly with macromolecular targets resulting in the formation of stable adducts providing depots for markers of exposure. The purpose of this study was to validate an analytical procedure for detection of HD-plasma protein adducts and to establish the utility of the method in an HD rat inhalation study. Calibration curves were prepared in human and rat plasma at six levels of HD (12.5 to 400 nM). Correlation coefficients for the mean data were 0.9987 for human and 0.9992 for rat plasma. The percent coefficient of variation (%CV) derived from the mean concentration data ranged from 0.53 to 14.1% in human (n = 5) and 0.57 to 10.63% in rat (n = 6) plasma. Intraday and interday precision and accuracy studies were conducted at three concentration levels (25, 150, 300 nM) to represent low, medium, and high concentrations of HD relative to those employed in the calibration curve. Precision and accuracy were assessed by determining %CV and % error, respectively. For intra- and interday studies, the %CVs and absolute % errors were less than 15%. The limits of quantitation were 20.88 nM for human and 16.73 nM for rat plasma. In animal studies, rats received nebulized HD at six doses. The data indicate a dose-dependent relationship between maximal plasma concentrations and dose administered (R(2) = 0.9728). Results from this study indicate an accurate, precise, and sensitive method. The method was useful in determining plasma protein adduct formation in a rat inhalation model.
Topics: Administration, Inhalation; Alkylation; Animals; Benzoates; Biomarkers; Blood Proteins; Calibration; Environmental Exposure; Environmental Monitoring; Gas Chromatography-Mass Spectrometry; Humans; Male; Mustard Gas; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Sodium Hydroxide; Sulfhydryl Compounds
PubMed: 18269791
DOI: 10.1093/jat/32.1.37 -
Annals of the New York Academy of... Apr 2010Exposure of tissues to sulfur mustard (SM) results in the formation of protein and nucleotide adducts that disrupt cellular metabolism and cause cell death. Subsequent... (Review)
Review
Exposure of tissues to sulfur mustard (SM) results in the formation of protein and nucleotide adducts that disrupt cellular metabolism and cause cell death. Subsequent pathologies involve a significant proinflammatory response, disrupted healing, and long-term defects in tissue architecture. Following ocular exposure, acute corneal sequelae include epithelial erosions, necrosis, and corneal inflammation. Longer term, a progressive injury becomes distributed throughout the anterior chamber, which ultimately causes a profound remodeling of corneal tissues. In many cases, debilitating and vision-threatening injuries reoccur months to years after the initial exposure. Preliminary data in humans suffering from chronic epithelial lesions suggest that thymosin beta4 (Tbeta4) may be a viable candidate to mitigate acute or long-term ocular SM injury. To evaluate therapeutic candidates, we have developed a rabbit ocular exposure model system. In this paper, we report molecular, histological, ultrastructural, and clinical consequences of rabbit ocular SM injury, which can be used to assess Tbeta4 efficacy, including timepoints at which Tbeta4 will be assessed for therapeutic utility.
Topics: Animals; Cornea; Eye; Eye Injuries; Humans; Male; Mice; Mustard Gas; Necrosis; Physiological Phenomena; Rabbits; Thymosin; Wound Healing
PubMed: 20536452
DOI: 10.1111/j.1749-6632.2010.05491.x -
Philadelphia Medicine Oct 1946
Topics: Anemia; Gas Poisoning; Gases; Humans; Mustard Gas; Sulfides
PubMed: 20274222
DOI: No ID Found -
The Journal of Organic Chemistry Nov 1946
Topics: Amino Acids; Mustard Gas; Peptides; Sulfides
PubMed: 20282491
DOI: 10.1021/jo01176a008 -
Journal of Analytical Toxicology 1985A procedure for the semi-quantitative determination of thiodiglycol, a metabolite of the vesicant mustard gas, in urine has been developed. Thiodiglycol was converted...
A procedure for the semi-quantitative determination of thiodiglycol, a metabolite of the vesicant mustard gas, in urine has been developed. Thiodiglycol was converted into mustard gas using concentrated HCl at temperatures close to 100 degrees C. The headspace of the solution containing mustard gas, was trapped on an adsorption tube filled with Tenax-GC which was subsequently analyzed by gas chromatography/mass spectrometry. Using 10 mL of urine, a detection limit of a few ng/mL of thiodiglycol was achieved. The procedure was applied to urine samples obtained from Iranian patients who were the alleged victims of an attack by chemical warfare agents (probably mustard gas). A number of control samples were investigated as well. Thiodiglycol was found in the urine of the Iranian patients in concentrations varying between 3 and 140 ng/mL. However, the detection of thiodiglycol in concentrations up to 55 ng/mL in control samples excluded the unambiguous verification of the use of mustard gas against the Iranian patients.
Topics: Adult; Chemical Warfare; Female; Humans; Hydrolysis; Iran; Male; Mustard Compounds; Mustard Gas; Sulfhydryl Compounds
PubMed: 4079337
DOI: 10.1093/jat/9.6.254 -
Archivos de La Sociedad Espanola de... Dec 2016
Topics: Chemical Warfare Agents; Eye Injuries; History, 20th Century; Humans; Mustard Gas; World War I
PubMed: 26923063
DOI: 10.1016/j.oftal.2016.01.026 -
Journal of Analytical Toxicology 2008An analytical method for determining exposure to 2,2'-dichlorodiethyl sulfide (sulfur mustard, HD) has been enhanced. The method is based on the cleavage of adducted HD...
An analytical method for determining exposure to 2,2'-dichlorodiethyl sulfide (sulfur mustard, HD) has been enhanced. The method is based on the cleavage of adducted HD (protein-hydroxyethylthioethyl esters) to produce thiodiglycol. Following cleavage, a deuterated internal standard is added, and the analytes are extracted, derivatized, and analyzed by gas chromatography-negative ion chemical ionization-mass spectrometry. Inclusion of a concentration step, addition of solid sodium bicarbonate to neutralize excess derivatization reagent, and optimization of method and instrument conditions provided dramatic increases in signal-to-noise ratio. A five-day precision and accuracy study was conducted, including interday and intraday unknown analysis. Linearity was verified by a R(2) > 0.9995 for all five curves evaluated. The precision and accuracy of the assay were demonstrated to be excellent by evaluation of the interday and intraday unknown samples (< 10% relative standard deviation and relative error in most cases). Statistical treatment of the method blanks and calibration results demonstrated a reduction in the limit of quantitation from 25 nM (HD, human plasma, in vitro) to 1.56 nM. Sample and calibration stability through the analytical sequence was established by the inclusion of continuing calibration verification standards (< 5% error). Short-term sample stability was verified by reinjection of a calibration set after 18 days (R(2) = 0.9997). Quantitative agreement with the previous method was supported by the analysis of a 50 nM standard protein sample (HD, rat plasma) with both methodologies (< 1% error).
Topics: Alkylation; Animals; Benzoates; Biomarkers; Blood Proteins; Calibration; Environmental Exposure; Environmental Monitoring; Gas Chromatography-Mass Spectrometry; Humans; Mustard Gas; Rats; Reproducibility of Results; Sodium Hydroxide; Sulfhydryl Compounds
PubMed: 18269790
DOI: 10.1093/jat/32.1.31 -
Journal of the American Chemical Society May 1948
Topics: Humans; Mustard Gas
PubMed: 18861835
DOI: 10.1021/ja01185a504 -
Environmental Science and Pollution... Oct 2021Chemical warfare (CW) agents are toxic synthetic chemicals that affect human's health, and sulfur mustard (SM) is a well-known chemical weapon that caused deaths of... (Review)
Review
Chemical warfare (CW) agents are toxic synthetic chemicals that affect human's health, and sulfur mustard (SM) is a well-known chemical weapon that caused deaths of victims. The lung is the main target of SM exposure, and there are no definitive therapeutic modalities for lung injury induced by this agent. The possible therapeutic effects of medicinal plants and their active ingredients on lung injury induced by SM were reviewed in this article until the end of June 2021. Medicinal plants including Crocus sativus, Curcuma longa, Thymus vulgaris, Nigella sativa, and Zataria multiflora and also natural compounds showed therapeutic potential in improving of various features of lung injury induced by SM and other related chemical agents. Several studies showed therapeutic effects of some medicinal plants and natural products on lung inflammation, oxidative stress, and immune responses in experimental studies in SM-induced lung injury. In addition, clinical studies also showed the effect of medicinal plants and natural compounds on respiratory symptoms, pulmonary function tests (PFTs), and inflammatory markers. The therapeutic effects of medicinal plants and natural products on lung disorder induced by SM and related chemical agents were shown through amelioration of various features of lung injury.
Topics: Humans; Lung; Mustard Gas; Plants, Medicinal
PubMed: 34382165
DOI: 10.1007/s11356-021-15697-2 -
Chemico-biological Interactions 1983Reaction of the toxic and mutagenic alkylating agent mustard gas with DNA of the yeast Saccharomyces cerevisiae was analyzed qualitatively and quantitatively. Within the...
Reaction of the toxic and mutagenic alkylating agent mustard gas with DNA of the yeast Saccharomyces cerevisiae was analyzed qualitatively and quantitatively. Within the dose range tested (2 X 10(-5)-2 X 10(-3) M) DNA in vivo is alkylated dose-proportionally. DNA alkylation and relative distribution of purine derivatives are not influenced by the cell's sensitivity towards the mutagen. At LD37 (4.4 X 10(-4) M) the wild type contains 44 300 purine derivatives: 9200 3-alkyladenines (20%), 29600 7-alkylguanines (67%) and 5500 diguaninyl derivates (13%) per genome. In sensitive strains the number of derivates per genome at LD37 is reduced according to the dose reduction factor. Alkylation at the position O6 of guanine by mustard gas cannot be shown, the method's limit of detection being 0.3% amongst purine derivates.
Topics: Alkylation; Chemical Phenomena; Chemistry; Chromatography; DNA Repair; DNA, Fungal; Mustard Compounds; Mustard Gas; Saccharomyces cerevisiae
PubMed: 6342826
DOI: 10.1016/0009-2797(83)90127-8