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
Following an accidental human exposure to a vesicating agent, plasma samples were analyzed for specific biomarkers of sulfur mustard. One individual suffered chemical burns over 6.5% of the body surface area and required hospitalization; the second individual developed a single, small blister. Plasma specimens from both individuals were examined using two different assays. The first assay targeted sulfur mustard adducts to cysteine-34 of albumin using affinity chromatography, enzyme digestion, and analysis of the alkylated peptide fragment using liquid chromatography-tandem mass spectrometry. The second assay targeted alkylation sites of glutamic and aspartic acids of plasma proteins. Following precipitation of plasma proteins, the sulfur mustard adducts were cleaved from the protein using base, derivatized, and analyzed using gas chromatography-mass spectrometry. Samples obtained over a 42-day period from the individual requiring hospitalization produced positive results for sulfur mustard adducts using both assays. Observed levels of the sulfur mustard biomarker decreased by approximately 75% between days 2 and 42 for both assays. Samples obtained over a six-day period from the individual with a single, small blister produced positive results for the albumin adduct assay. Observed levels were much lower than levels from the hospitalized patient. Blood samples from suspected human exposures to sulfur mustard have only rarely been made available for analysis by sensitive and specific laboratory assays. The data presented here add significantly to the small database of information that currently exists on human biomarkers of sulfur mustard exposure, linking a well-documented exposure event with levels of plasma protein adducts.
Hexaphenylcarbodiphosphorane when treated with manganese pentacarbonyl bromide or rhenium pentacarbonyl bromide gives M(Br)(CO)4(Ce=CPP1i3), M = Mn or Re, and triphenylphosphine oxide. This is the first reported instance of a Wittig type reaction on a metal-coordinated carbonyl group. X-Ray diffraction studies show that an acetylide ligand is formed instead of the expected olefin. In contrast to this behavior, normal Wittig reagents give ylide carbene adducts with metal carbonyls of chromium, tungsten, and iron. These do not the y(C=C), (C6H5)3P+C=C: ~, moiety in the complex.
A gas chromatography-mass spectrometry method for determining exposure to the chemical warfare agent 2,2'-dichlorodiethyl sulfide (sulfur mustard; HD) has been developed. The technique is based upon quantitating thiodiglycol (TDG) released from blood protein adducts that are formed upon exposure to HD. Protein was precipitated from plasma, whole blood, or packed red blood cells (RBCs) and then treated with sodium hydroxide to liberate protein-bound TDG. The TDG was derivatized with pentafluorobenzoyl chloride that enabled sensitive detection by negative-ion chemical ionization. Octadeuterothiodiglycol was used as an internal standard. Exposure of human plasma to HD (25 nM to 400 nM) resulted in a linear relationship (r2 = 0.9995) between HD concentration and released TDG levels with means ranging from 2.0 to 38 pg/mg protein. The coefficients of variation expressed as a percentage for the data points ranged from 2 to 11.5%. The application of this procedure was demonstrated in two HD animal exposure models. African green monkeys (Chlorocebus aethiops) were exposed intravenously to 1 mg/kg HD, and TDG levels in blood samples were analyzed out to 45 days post-exposure. Mean TDG levels were determined to be 220 pg/mg protein on day 1 and declined to 10 pg/mg protein on day 45. Yorkshire cross pigs (Sus scrofa) were cutaneously exposed to neat liquid HD, and TDG levels in plasma were determined out to 21 days following exposure. Mean TDG levels were found to be 60 pg/mg protein on day one and decreased to an average of 4 pg/mg protein on day 21. The data from this study indicate that the assay is sensitive and provide a relatively simple approach to assay TDG cleaved from blood proteins at relatively long time frames (21-45 days) after HD exposure. The utility of the method has been demonstrated in vivo in a non-human primate and pig HD exposure model.
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