Untargeted and targeted analysis of sarin poisoning biomarkers in rat urine by liquid chromatography and tandem mass spectrometry.

Chemical warfare agents continue to pose a real threat to humanity, despite their prohibition under the Chemical Weapons Convention. Sarin is one of the most toxic and lethal representatives of nerve agents. The methodology for the targeted analysis of known sarin metabolites has reached great heights, but little attention has been paid to the untargeted analysis of biological samples of victims exposed to this deadly poisonous substance. At present, the development of computational and statistical methods of analysis offers great opportunities for finding new metabolites or understanding the mechanisms of action or effect of toxic substances on the organism. This study presents the targeted LC-MS/MS determination of methylphosphonic acid and isopropyl methylphosphonic acid in the urine of rats exposed to a non-lethal dose of sarin, as well as the untarget urine analysis by LC-HRMS. Targeted analysis of polar acidic sarin metabolites was performed on a mixed-mode reversed-phase anion-exchange column, and untargeted analysis on a conventional reversed-phase C18 column. Isopropyl methylphosphonic acid was detected and quantified within 5 days after subcutaneous injection of sarin at a dose of 1/4 LD50. A combination of generalized additive mixed models and dose-response analysis with database searches using accurate mass of precursor ions and corresponding MS/MS spectra enabled us to propose new six potential biomarkers of biological response to exposure. The results confirm the well-known fact that sarin poisoning has a significant impact on the victims' metabolome, with inhibition of acetylcholinesterase being just the first step and trigger of the complex toxicodynamic response.

Improving Quantification of tabun, sarin, soman, cyclosarin, and sulfur mustard by focusing agents: A field portable gas chromatography-mass spectrometry study.

Commercial gas chromatograph-mass spectrometers, one of which being Inficon's HAPSITE® ER, have demonstrated chemical detection and identification of nerve agents (G-series) and blistering agents (mustard gas) in the field; however most analyses relies on self-contained or external calibration that inherently drifts over time. We describe an analytical approach that uses target-based thermal desorption standards, called focusing agents, to accurately calculate concentrations of chemical warfare agents that are analyzed by gas chromatograph-mass spectrometry. Here, we provide relative response factors of focusing agents (2-chloroethyl ethyl sulfide, diisopropyl fluorophosphate, diethyl methylphosphonate, diethyl malonate, methyl salicylate, and dichlorvos) that are used to quantify concentrations of tabun, sarin, soman, cyclosarin and sulfur mustard loaded on thermal desorption tubes (Tenax® TA). Aging effects of focusing agents are evaluated by monitoring deviations in quantification as thermal desorption tubes age in storage at room temperature and relative humidity. The addition of focusing agents improves the quantification of tabun, sarin, soman, cyclosarin and sulfur mustard that is analyzed within the same day as well as a 14-day period. Among the six focusing agents studied here, diisopropyl fluorophosphate has the best performance for nerve agents (G-series) and blistering agents (mustard gas) compared to other focusing agents in this work and is recommended for field use for quantification. The use of focusing agent in the field leads to more accurate and reliable quantification of Tabun (GA), Sarin (GB), Soman (GD), Cyclosarin (GF) and Sulfur Mustard (HD) than the traditional internal standard. Future improvements on the detection of chemical, biological, radiological, nuclear, and explosive materials (CBRNE) can be safely demonstrated with standards calibrated for harmful agents.

[The urgency of the application of the medical sanitary passport in the system for chemical safety in the areas of location of high-risk chemical facilities in the Russian Federation].

The main provisions concerning the need for a creation of medical and sanitary passport for territories in the protective measures zones (PMZ) of storage facilities and facilities for the destruction of chemical weapons (FDCW) are presented in the article. The assessment of results of certification of the territory of PMZ and FDCW in "Maradykovsky" in the Kirov region has been done.

Provisional Advisory Levels (PALs) for phosgene (CG).

The Provisional Advisory Level (PAL) protocol was applied to estimate inhalation exposure limits for phosgene (CG). Three levels (PAL 1, PAL 2, and PAL 3), distinguished by severity of toxic effects, are developed for 24-hour, 30-day, 90-day, and 2-year durations of potential drinking water and inhalation exposures for the general public. For background on the PAL program and a description of the methodology used in deriving PALs, the reader is referred to accompanying papers in this Supplement. Data on humans are limited to occupational exposures or accounts from the use of phosgene as a chemical warfare agent in World War I. Animal studies with phosgene show a steep dose-response curve for pulmonary edema and mortality, with little species variability in effects. Although immediately upon exposure lacrimation and upper respiratory irritation can occur, the main effect in the target organ, a progressive pulmonary edema, occurs after a latency period of 1-24 hours. PAL estimates were approved by the Expert Consultation Panel for Provisional Advisory Levels in May 2007. Exposure limits for oral exposure to CG are not developed due to insufficient data. PAL estimates for inhalation exposure to CG are presented: The 24-hour PAL values for severity levels 1, 2, and 3 are 0.0017, 0.0033 and 0.022 ppm, respectively. The 30- and 90-day PAL values are 0.0006 and 0.0012 ppm for the PAL 1 and 2 values, respectively. These inhalation values were also accepted as the 2-year PAL 1 and 2 values because severity of lesions in the key study did not increase when exposures were extended from 4 weeks to 12 weeks. Data were not available for deriving 30-day, 90-day, and 2-year PAL 3 values.

Health-based Provisional Advisory Levels (PALs) for homeland security.

The Homeland Security Presidential Directive #8 (HSPD-8) for National Emergency Preparedness was issued to " establish policies to strengthen the preparedness of the United States to prevent and respond to threatened or actual domestic terrorist attacks, major disasters, and other emergencies by requiring a national domestic all- hazards preparedness goal. "In response to HSPD-8 and HSPD-22 (classified) on Domestic Chemical Defense, the US Environmental Protection Agency (US EPA) National Homeland Security Research Center (NHSRC) is developing health-based Provisional Advisory Levels (PALs) for priority chemicals (including chemical warfare agents, pesticides, and toxic industrial chemicals) in air and drinking water. PALs are temporary values that will neither be promulgated, nor be formally issued as regulatory guidance. They are intended to be used at the discretion of risk managers in emergency situations. The PAL Program provides advisory exposure levels for chemical agents to assist in emergency planning and response decision-making, and to aid in making informed risk management decisions for evacuation, temporary re-entry into affected areas, and resumed-use of infrastructure, such as water resources. These risk management decisions may be made at the federal, state, and local levels. Three exposure levels (PAL 1, PAL 2, and PAL 3), distinguished by severity of toxic effects, are developed for 24-hour, 30-day, 90-day, and 2-year durations for potential exposure to drinking water and ambient air by the general public. Developed PALs are evaluated both by a US EPA working group, and an external multidisciplinary panel to ensure scientific credibility and wide acceptance. In this Special Issue publication, we present background information on the PAL program, the methodology used in deriving PALs, and the technical support documents for the derivation of PALs for acrylonitrile, hydrogen sulfide, and phosgene.

Biologists napping while work militarized.

As researchers discover more agents that alter mental states, the Chemical Weapons Convention needs modification to help ensure that the life sciences are not used for hostile purposes, says Malcolm Dando.

Investigation of compound-independent calibration and partial molecular formula determination by gas chromatography-atomic-emission detection for characterisation of organophosphorus and organosulfur agents related to the chemical weapons convention.

Atomic-emission detection (AED) is a technique particularly-well suited to screening complex samples for multiple compounds containing heteroatoms such as phosphorus, sulfur, or nitrogen, which are especially relevant in verification of chemical disarmament. Among other GC detectors, AED has unique characteristics such as compound-independent calibration and possible raw-formula determination. Because contradictory results have been reported on these points, we set up a study with the objectives not only of applying these techniques to chemical weapons convention-related chemicals but of determining under which conditions they would yield satisfactory results. The extensive data collected in this study are evidence that the response of the detector, particularly for the phosphorus line, is very dependent on the molecular mass and concentration of the chemicals analysed whereas molecular structure seems to have less effect on the AED signal. Most interestingly, compound-independent calibration and subsequent partial molecular formula determination usually seem satisfactory when the reference compounds used to calibrate the system have GC retention times and molecular masses close to those of the unknown analytes (whose molecular mass may be determined by GC-CI-MS). We therefore suggest the use of a reference set of compounds covering a large chromatographic window, which enables the selection, within this set, of the most appropriate reference compound for calibration and for determination of the raw formula of an unknown analyte. For optimal performance, the use of a new discharge tube is also recommended.

Contaminación por agentes químicos / Contamination by chemical agents

La contaminación por productos químicos es una situación clínica cuyo manejo precisa de una serie de conocimientos muy concretos por parte de los médicos de emergencias, al tener que conocer los tipos de agentes químicos más frecuentes y su mecanismo de acción. Este tipo de contaminación exige la existencia de unos planes concretos de actuación en el ámbito hospitalario y en coordinación con los mecanismos extrahospitalarios de emergencias. Al riesgo que supone el estar diariamente rodeados de productos químicos a escala industrial, con riesgo de escapes y accidentes durante su transporte e incluso en los domicilios, se une la posibilidad de utilización de diversos agentes químicos como armas de destrucción masiva, tanto en conflictos bélicos, como en actos terroristas (AU)

Rapid screening of aqueous chemical warfare agent degradation products: ambient pressure ion mobility mass spectrometry.

The use of electrospray ionization ambient pressure ion mobility spectrometry with an orthogonal reflector time-of-flight mass spectrometer to analyze chemical warfare (CW) degradation products from aqueous environmental samples has been demonstrated. Certified reference materials of analytical standards for the detection of Schedule 1, 2, or 3 toxic chemicals or their precursors as defined by the chemical warfare convention treaty verification were used in this study. A combination of six G/V-type nerve and four S-type vesicant related CW agent degradation products were separated with baseline resolution by this instrumental technique. Analytical figures of merit for each CW degradation product were determined. In some cases, reduced mobility constants (K0) have been reported for the first time. linear response ranges for the selected CW degradation products were found to be generally approximately 2 orders of magnitude, where the overall dynamic response ranges were found to extend to 4 orders of magnitude. Limits of detection for five of the nine chemical products tested were found to be less than 1 ppm. To demonstrate the potential of this instrumental method with complex mixtures, four CW degradation products were separated and detected from a spiked Palouse River water sample in less than 1 min. Finally, a homologous series of n-alkylamines were used as baseline reference standards, producing a mobility/mass trend line to which the CW degradation products could be compared. Comparison of these products in this manner is expected to reduce the number of false positive/negative responses.

Evaluation of risk assessment guideline levels for the chemical warfare agents mustard, GB, and VX.

The U.S. Army has estimated acute lethality guideline levels for inhalation of the chemical warfare agents mustard, GB, and VX. These levels are expressed as dosages measured in milligram-minutes per cubic meter (mg-min/m(3)). The National Advisory Council has also proposed acute emergency guideline levels (AEGLs) for the agents. The AEGLs are threshold exposure limits for the general public for mild effects, serious adverse effects, and lethality. They are expressed as air concentrations (in units of mg/m(3)) and are applicable to emergency exposure periods ranging from 10 min to 8 h. The report discusses strengths and deficiencies in the levels, important parameters (i.e., exposure time, breathing rate) that need to be explicitly addressed in deriving the guideline levels, and possible impacts that could result from using AEGLs instead of guideline dosages in future assessments.

Formación en materia NBQ para el personal sanitario de las Fuerzas Armadas

Dadas las características y necesidades particulares que plantearía cualquier agresión en ambiente NBQ, se hace cada vez más necesario que nuestro personal sanitario (médicos, veterinarios, farmacéuticas, DUES-ATS) estén preparados para afrontar esta situación. El personal sanitario debe tener los conocimientos necesarios para ser capaz de protegerse de los agresivos NBQ, tanto ellos mismos, como a las bajas y al propio material sanitario y llevar a cabo, de acuerdo con los últimos conocimientos en ciencia y tecnología, todas las medidas necesarias para mantener y restaurar la salud de todo el personal expuesto a un ambiente NBQ. Haciendo hincapié en la formación del personal y prevención. Es imprescindible que todo el personal sanitario conozca y cumpla los niveles básicos relacionados con el campo NBQ. Cada uno de los integrantes del Cuerpo Militar de Sanidad, a su nivel y de acuerdo a su responsabilidad establecerán los criterios mínimos para poder adecuar los medios a la consecución de la misión (AU)