Biomonitoring of exposure to chemical warfare agents: a review.
ABSTRACT In this report an overview of the methods currently available for detection of exposure to a number of chemical warfare agents (CWA), i.e., sulfur mustard, lewisite and nerve agents, is presented. Such methods can be applied for various purposes, e.g., diagnosis and dosimetry of exposure of casualties, confirmation of nonexposure, verification of nonadherence to the Chemical Weapons Convention, health surveillance, and forensic purposes. The methods are either based on mass spectrometric or immunochemical analysis of CWA adducts with DNA or proteins or based on mass spectrometric analysis of urine or plasma metabolites that result from hydrolysis and/or glutathione conjugation. Several of the methods have been successfully applied to actual cases.
- SourceAvailable from: Judit Marsillach Lopez[show abstract] [hide abstract]
ABSTRACT: Organophosphorus (OP) compounds include a broad group of toxic chemicals such as insecticides, chemical warfare agents and antiwear agents. The liver cytochromes P450 bioactivate many OPs to potent inhibitors of serine hydrolases. Cholinesterases were the first OP targets discovered and are the most studied. They are used to monitor human exposures to OP compounds. However, the assay that is currently used has limitations. The mechanism of action of OP compounds is the inhibition of serine hydrolases by covalently modifying their active-site serine. After structural rearrangement, the complex OP inhibitor-enzyme is irreversible and will remain in circulation until the modified enzyme is degraded. Mass spectrometry is a sensitive technology for analyzing protein modifications, such as OP-adducted enzymes. These analyses also provide some information about the nature of the OP adduct. Our aim is to develop high-throughput protocols for monitoring OP exposures using mass spectrometry.Chemico-biological interactions 11/2012; · 2.46 Impact Factor
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ABSTRACT: In order to gain preliminary knowledge about the threat to marine ecosystems due to leakage of chemical warfare agents (CWAs) and other pollutants from rusting bombshells on the seabed, a case study was conducted in a dumping area in the southern Adriatic Sea (depth 200–300m). Following electroacoustic and magnetometric surveys of the CWA dumping area, an integrated ecotoxicological approach was used. This approach was based on analysis of CWA residues and their metabolites, including arsenic, in sediment and organisms, as well as multimarker methodology including the Health Assessment Index, histological lesion analysis and enzyme assays. Two sentinel species were selected, the blackbelly rosefish [Helicolenus dactylopterus (Delaroche, 1809)] and the European conger (Conger conger L., 1758). Sediment analysis revealed the presence of CWA degradation products, including 1-4-thioxane and 1-4-dithiane. Tissues of fish from the CWA dumping site showed higher levels of arsenic than those from the reference site. Neither CWAs nor their metabolites were detected in fish tissues. Arsenic levels recorded in blackbelly rosefish were well above those reported for other fish species from the southern Adriatic, much higher than the FDA limit for food (2.6mgkg−1) and close to the LD50 calculated for mammals (20mgkg−1 body weight). The presence of pollutants in the CWA dumping site was also confirmed by pathological lesions in both species and EROD activity, two to three times higher than in fish from the reference site (16.45±8.08 and 8.05±5.87pmolmin−1mg protein−1 in blackbelly rosefish and 269±24.92 and 78.71pmolmin−1mgprotein−1 in European conger, respectively). Cholinesterase activity seemed unaffected in muscle of both species, whereas in brain they were one-third of those recorded in fish from the reference site (14.22±10.05 and 72.87nmolmin−1mgprotein−1, respectively). This suggests that acetylcholinesterase is sensitive to CWAs. In conclusion, the agreement of all the chemical and biological parameters investigated suggests that the integrated ecotoxicological approach used is appropriate to reveal the presence and biological effects of CWAs in the marine ecosystem.Marine Biology 04/2012; 149(1):17-23. · 2.47 Impact Factor
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ABSTRACT: BACKGROUND: To date, sulphur mustard (SM) cutaneous toxicity has been commonly assessed on account of several animal models such as pigs and weanling pigs. Few experiments however, have been carried out on mice so far. In this study, we aimed at quantifying spontaneous wound healing processes after SM exposure on a SKH-1 mouse model through non-invasive methods over an extended period of time. METHODS: Animals were exposed to 10 μL net SM in a vapor cup system. Measurements of barrier function (Transepidermal water loss), elasticity, skin color exposed to SM vapors were determined by evaporimetry, cutometer and image analysis on 23 animals up to 28 days. Results were subsequently correlated with histological and biochemical analyses. RESULTS: The TEWL parameter stands as a top-ranking criterion to keep track of skin barrier restoration after SM cutaneous intoxication in our SKH-1 mouse model. The R2 and R6 elasticity parameters or L° for the skin color exhibited their ability to be restored after 28 days of SM exposure. CONCLUSION: Our findings suggest that bio-engineering methods are eligible to evaluate new treatments on SM-induced skin SKH-1 mouse lesions, thus making an allowance for less invasive methods such as histological, genomic or proteomic approaches.Skin Research and Technology 06/2012; · 1.41 Impact Factor