Biomonitoring of Exposure to Chemical Warfare Agents: A Review

Noort, Daan; Benschop, H. P.; Black, Robin M.

doi:10.1006/taap.2002.9449

Cited by 240 publications

(131 citation statements)

References 71 publications

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“…The likely, but not proven, major source of the reactivated agents was the agent adduct of plasma CaE[ 13 ' 15 -18 ' 20 1 rather than BuChE. 1 7 '8 1 The soman adduct of BuChE ages too rapidly to be a significant source of reactivated soman in this study.t 1 ' 12 ' Relatively high levels of reactivated agent in kidney and lung tissue compared to heart and liver tissue ( Figure 1) were consistent with prior measurements of soman deposition in tissue using radiolabels. 121 Even though the liver is usually considered the major source of CaE, the plasma CaE was likely to be the major reactant in forming the CaE-agent adducts.…”

Section: Discussionmentioning

confidence: 99%

The Application of the Fluoride Reactivation Process to the Detection of Sarin and Soman Nerve Agent Exposures in Biological Samples

Adams¹,

Capacio²,

Smith³

et al. 2004

Drug and Chemical Toxicology

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information The fluoride reactivation process was evaluated for measuring the level of sarin or soman nerve agents reactivated from substrates in plasma and tissue from in vivo exposed guinea pigs (Cava porcellus), in blood from in vivo exposed rhesus monkeys (Macaca mulatta), and in spiked human plasma and purified human albumin. Guinea pig exposures ranged from 0.05 to 44 LD5 0 , and reactivated nerve agent levels ranged from 1.0 ng/mL in plasma obtained from 0.05 LD 50 sarinexposed guinea pigs to an average of 147 ng/g in kidney tissue obtained from two 2.0 LD 50 soman-exposed guinea pigs. Positive dose-response relationships were observed in all low-level, 0.05 to 0.4 LD 50 , exposure studies. An average value of 2.4 ng/mL for reactivated soman was determined in plasma obtained from two rhesus monkeys three days after a 2 LD 50 exposure. Of the five types of guinea pig

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Section: Discussionmentioning

confidence: 99%

The Application of the Fluoride Reactivation Process to the Detection of Sarin and Soman Nerve Agent Exposures in Biological Samples

Adams¹,

Capacio²,

Smith³

et al. 2004

Drug and Chemical Toxicology

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“…A short supply of acetylcholine is associated with Alzheimer's disease [3,4]. Due to their toxicological activity some OPs have been used also as Chemical Warfare Agents (CWAs) [5,6].…”

Section: Introductionmentioning

confidence: 99%

An acetylcholinesterase biosensor for determination of low concentrations of Paraoxon and Dichlorvos

et al. 2011

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The characterization of an economic and ease-to-use carbon paste acetylcholinesterase (AChE) based biosensor to determine the concentration of pesticides Paraoxon and Dichlorvos is discussed. AChE hydrolyses acetylthiocholine (ATCh) in thiocoline (TC) and acetic acid (AA). When AChE is immobilized into a paste carbon working electrode kept at +410 mV vs. Ag/AgCl electrode, the enzyme reaction rate using acetylthiocholine chloride (ATCl) as substrate is monitored as a current intensity. Because Paraoxon and Dichlorvos inhibit the AChE reaction, the decrease of the current intensity, at fixed ATCl concentration, is a measure of their concentration. Linear calibration curves for Paraoxon and Dichlorvos determination have been obtained. The detection limits resulted to be 0.86 ppb and 4.2 ppb for Paraoxon and Dichlorvos, respectively, while the extension of the linear range was up 23 ppb for the former pesticide and up to 33 ppb for the latter. Because the inhibited enzyme can be reactivated when immediately treated with an oxime, the biosensor reactivation has been studied when 1,1 0 -trimethylene bis 4-formylpyridinium bromide dioxime (TMB-4) and pyridine 2-aldoxime methiodide (2-PAM) were used. TMB-4 resulted more effective. The comparison with the behavior of similar AChE based biosensors is also presented.

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“…There was a peak overlap between native AChE and sarin-inhibited AChE upon MS. 16) To overcome inefficient mass separation between natural and adduct proteins, liquid chromatography (LC)-MS with protease digestion has been developed. Barak et al 16) have demonstrated the direct detection of sarin and soman adducts of human recombinant AChE using matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) MS. Noort et al 17) have established the biomonitoring method of CWA exposure by detecting adducts of biological macromolecules using LC-MS. Fidder et al 18) have reported the analysis of human BuChE adducts using LC-MS to verify nerve gas exposure, by which human BuChE was purified by procainamide affinity chromatography, and the active center nonapeptide was detected as an adduct marker after pepsin digestion. Other BuChE-Organization for the Prohibition of Chemical Weapons (OPCW) Schedule 1 nerve gas adducts have also been analyzed.…”

Section: Direct Analysismentioning

confidence: 99%

Mass Spectrometric Identification of Chemical Warfare Agent Adducts with Biological Macromolecule for Verification of Their Exposure

Tsuge

Seto

2009

JOURNAL OF HEALTH SCIENCE

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Exposure to chemical warfare agents (CWAs) can be verified by detecting their degradation products in biological samples. However, the half-lives of these CWA degradation products in the body are short. CWAs are known to combine with biological macromolecules and the covalently bound compounds are called adducts. The residence time of adducts in the human body is longer than that of the corresponding CWA degradation products. Therefore, development of analytical methods to detect these adducts is a more realistic way of verifying CWA exposure. In this mini review, we describe the present state of research on analytical methods for identifying CWA adducts, and mainly introduce our research on nerve gas adducts using a direct method. Novel analytical methods for verifying low level exposure to nerve gases use liquid chromatography-mass spectrometry (LC-MS). Butyrylcholinesterase (BuChE) has been purified by affinity chromatography and sodium dodecylsulfate poly-acrylamide gel electrophoresis. The purified enzyme is inhibited by nerve gases (sarin, VX and soman) and digested by chymotrypsin, and then the peptides are analyzed by LC-MS and LC tandem MS. The peptide fragment that is combined with nerve gas is detected by LC-MS. Furthermore, the chemical structure of the adduct peptide characterized by MS provides structural information about the analyte. The detection limit of BuChE or BuChE adduct is estimated at 4 ng/injection (53 fmol/injection). If at least 1% of BuChE activity is inhibited by nerve gas, the adduct can be detected at a level of 1% BuChE inhibition in the victim's serum.

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Biomonitoring of Exposure to Chemical Warfare Agents: A Review

Cited by 240 publications

References 71 publications

The Application of the Fluoride Reactivation Process to the Detection of Sarin and Soman Nerve Agent Exposures in Biological Samples

The Application of the Fluoride Reactivation Process to the Detection of Sarin and Soman Nerve Agent Exposures in Biological Samples

An acetylcholinesterase biosensor for determination of low concentrations of Paraoxon and Dichlorvos

Mass Spectrometric Identification of Chemical Warfare Agent Adducts with Biological Macromolecule for Verification of Their Exposure

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