History and perspectives of bioanalytical methods for chemical warfare agent detection

Black, Robin M.

doi:10.1016/j.jchromb.2009.11.025

Cited by 82 publications

(39 citation statements)

References 74 publications

(95 reference statements)

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“…VX, which is less reactive than other WNAs, formed an adduct in human plasma in vitro only at high concentrations (Williams et al, 2007;Black, 2010;Black and Read, 2013). Tyrosine adducts were less sensitive than ChE as biomarkers with respect to exposure levels but were more stable and did not undergo an aging reaction such as OP binding to serine esterases (Read et al, 2010).…”

Section: Protein Bindingmentioning

confidence: 97%

“…Within the first minute, approximately half of the labeled sarin was in the form of IMPA. The highest concentrations of sarin and its (Nakajima et al, 1998;Katagi et al, 1999;Jokanović, 2001Jokanović, , 2009Evans et al, 2008;Black, 2010;Tenberken et al, 2010;Reiter et al, 2011;Black and Read, 2013;Kranawetvogl et al, 2013). metabolites were found in the kidneys. Lower concentrations of IMPA and MPA were detected in the liver, suggesting a minor role for the liver in detoxification of sarin.…”

Section: Chemical Aspects Of Biotransformation Of Wnasmentioning

confidence: 98%

“…The metabolites of tabun EDMPA and EPCA (Figure 59.1) are apparently unstable, whereas the EPA is an excretion metabolite of tabun as well as of certain pesticides and plasticisers (Tenberken et al, 2010;Black and Read, 2013). The final metabolite of tabun is a phosphate (Black, 2010). Toxicity data are available only for a limited subset of the tabun degradation products.…”

Section: Chemical Aspects Of Biotransformation Of Wnasmentioning

confidence: 99%

“…There are certain characteristics of VX that make the agent different from G-agents, such as the following: VX is present in blood as protonated amine; it is hydrolyzed at a much slower rate than G-agents; it reacts more slowly with CarbE (because of its positively charged quaternary ammonium group) and A-esterases; and VX can be metabolized by other routes such as oxidation reactions at nitrogen and/or sulfur (Jokanović, 2009;Black, 2010). A few of the metabolic products may retain some anticholinesterase activity (such as EA2192) (Munro et al, 1999), but hydrolysis of one or more alkyl ester bonds of organophosphonic acids results in generally nontoxic alkyl methylphosphonic acids EMPA and MPA.…”

Section: Chemical Aspects Of Biotransformation Of Wnasmentioning

confidence: 99%

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Biotransformation of Warfare Nerve Agents

Jokanović¹

2015

Handbook of Toxicology of Chemical Warfare Agents

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Section: Protein Bindingmentioning

confidence: 97%

Section: Chemical Aspects Of Biotransformation Of Wnasmentioning

confidence: 98%

Section: Chemical Aspects Of Biotransformation Of Wnasmentioning

confidence: 99%

Section: Chemical Aspects Of Biotransformation Of Wnasmentioning

confidence: 99%

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Biotransformation of Warfare Nerve Agents

Jokanović¹

2015

Handbook of Toxicology of Chemical Warfare Agents

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“…nerve agents, SM). As the analytical detection of poisons traditionally has been a central issue in toxicological research, modern toxicology is able to provide substantial expertise and tools to improve the detection and quantification of CWA in environmental and tissue samples (Maurer 2007;Black 2010).…”

mentioning

confidence: 99%

Chemical warfare in the First World War: reflections 100 years later

Mangerich

Esser

2014

Arch Toxicol

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Methods for the Retrospective Detection of Exposure to Toxic Scheduled Chemicals: Analysis of Free Metabolites

Black

Read

Noort³

2000

Encyclopedia of Analytical Chemistry

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In cases of investigations into alleged use of chemical warfare agents, biomedical samples such as urine or blood may be collected from casualties for forensic analysis. Analysis of biomedical samples may also be undertaken for diagnostic purposes, to ensure appropriate medical treatment, and for occupational exposure monitoring, e.g. in workers engaged in demilitarization activities. Metabolites excreted in urine, or circulating in the blood, provide unequivocal biological markers of exposure. Metabolic pathways have been identified for the blister agent sulfur mustard and organophosphorus nerve agents. Sensitive analytical methods have been developed for the major metabolites, based on gas or liquid chromatography combined with single stage or tandem mass spectrometry. Methods developed primarily for application in investigations of alleged use of chemical warfare agents have focused on achieving low levels of detection combined with high selectivity. A significant trend over the last decade has been the development of higher throughput methods, aimed primarily at homeland security applications, e.g. in the case of terrorist use. Selected metabolites have been validated in cases of accidental or deliberate human exposure to sulfur mustard, and the nerve agents sarin and VX. Putative metabolites have been identified in animal studies for other nerve agents, nitrogen mustards, Lewisite and the incapacitant BZ. Phosgene and hydrogen cyanide have received much less attention with respect to retrospective identification of exposure in a chemical warfare context. Many analytical methods are available for metabolites of cyanide but significant background levels are present in the general population. A disadvantage of free metabolites is that they are relatively rapidly excreted. The window for identification following an exposure is estimated to be in the region of 14 days, depending on the severity of the exposure and the limit of detection of the analytical method. Covalent adducts with proteins and DNA may offer longer lived biomarkers of exposure.

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History and perspectives of bioanalytical methods for chemical warfare agent detection

Cited by 82 publications

References 74 publications

Biotransformation of Warfare Nerve Agents

Biotransformation of Warfare Nerve Agents

Chemical warfare in the First World War: reflections 100 years later

Methods for the Retrospective Detection of Exposure to Toxic Scheduled Chemicals: Analysis of Free Metabolites

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