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2. List of contributors

Author

Anadón, Arturo, primary, Andrys, Rudolf, additional, Avdonin, Pavel, additional, Bajgar, Jiri, additional, Balali-Mood, Mahdi, additional, Balszuweit, Frank, additional, Banerjee, Atrayee, additional, Bast, Cheryl B., additional, Belinskaia, Daria, additional, Bharti, Vijay K., additional, Bollinger, Claire E., additional, Casillas, Robert P., additional, Clark, Ryan, additional, Clarkson, Edward D., additional, Cole, Toby B., additional, Cope, Rhian B., additional, Coppock, Robert W., additional, Costa, Lucio G., additional, Dettbarn, Wolf-D., additional, Dlabkova, Alzbeta, additional, Doss, Robin B., additional, Dziwenka, Margitta M., additional, Estevez, Jorge, additional, Evans, Tim J., additional, Fink, John K., additional, Flora, Swaran J.S., additional, Furlong, Clement E., additional, Fusek, Josef, additional, Garrick, Jacqueline, additional, Gearhart, Jeffery M., additional, Gerecke, Donald R., additional, Glass-Mattie, Dana F., additional, Goel, Saryu, additional, Goncharov, Nikolay, additional, Gordon, Richard K., additional, Gray, Joshua P., additional, Grubic, Zoran, additional, Gulati, Kavita, additional, Gupta, Ramesh C., additional, Gwaltney-Brant, Sharon M., additional, Hamilton, Tracey A., additional, Harris, Kenneth J., additional, Hood, Darryl B., additional, Jakubowski, Edward M., additional, Jenkins, Richard, additional, Jett, David A., additional, Jiao, Yuqin, additional, John, Harald, additional, Johnson, Nathan H., additional, Jokanović, Milan, additional, Jun, Daniel, additional, Karakashev, Georgy, additional, Kassa, Jiri, additional, Katalinic, Maja, additional, Kehe, Kai, additional, Khlebnikova, Natalia, additional, Kodavanti, Urmila P., additional, Korf, Ekaterina, additional, Koryagina, Nadezhda, additional, Kovač, Bojan, additional, Krishna, Gopala, additional, Krishna, Mayur, additional, Kuca, Kamil, additional, Kumar, Dinesh, additional, Kuroiwa, Yukio, additional, Kuznetsov, Sergey, additional, Kuča, Kamil, additional, Larsen, Joseph C., additional, Leninskiy, Mikhail, additional, Liu, Jing, additional, Lochotzki, Heather, additional, Lockridge, Oksana, additional, Lockwich, Jordana, additional, Loganathan, Bommanna G., additional, Lončar-Stojiljković, Dragana, additional, Lushchekina, Sofya V., additional, Lyman, Megan E., additional, Maguire, Mark, additional, Makhaeva, Galina F., additional, Malik, Jitendra K., additional, Malinak, David, additional, Mars, Tomaz, additional, Marsillach, Judit, additional, Martínez-Larrañaga, María-Rosa, additional, Masson, Patrick, additional, Masunaga, Shigeki, additional, McCallister, Monique, additional, McCauley, Linda A., additional, McClellan, Roger O., additional, McNutt, Patrick M., additional, Meek, Edward C., additional, Merrill, Elaine, additional, Milanez, Sylvia, additional, Mindukshev, Igor, additional, Mis, Katarina, additional, Misik, Jan, additional, Murphy, Michael J., additional, Musilek, Kamil, additional, Nakajima, Tamie, additional, Nelson, Marian R., additional, Nepovimova, Eugenie, additional, Okumura, Tetsu, additional, Patocka, Jiri, additional, Pegan, Katarina, additional, Pejchal, Jaroslav, additional, Pirkmajer, Sergej, additional, Pita, René, additional, Pitt, Jason, additional, Pitt, Yiuka, additional, Platoff, Gennady E., additional, Pope, Carey N., additional, Radilov, Andrey, additional, Rahal, Anu, additional, Ramesh, Aramandla, additional, Ray, Arunabha, additional, Rembovskiy, Vladimir, additional, Rhoades, Raina, additional, Richardson, Rudy J., additional, Ristić, Dragana, additional, Robinson, Peter J., additional, Romero, Alejandro, additional, Ruark, Chris, additional, Salem, Harry, additional, Samchenko, Natalia, additional, Satoh, Tetsuo, additional, Savage, Russell E., additional, Savelieva, Elena, additional, Schopfer, Lawrence M., additional, Sciuto, Alfred M., additional, Seto, Yasuo, additional, Shakarjian, Michael P., additional, Shmurak, Vladimir, additional, Skarka, Adam, additional, Škrbić, Ranko, additional, Sogorb, Miguel, additional, Spriggs, Shardell M., additional, Srivastava, Sakshi, additional, Steinritz, Dirk, additional, Stojiljković, Miloš P., additional, Tewari-Singh, Neera, additional, Thiermann, Horst, additional, Thokchom, Suresh Kumar, additional, Thompson, Larry J., additional, Ukolov, Anton, additional, Valerio, Luis G., additional, van der Schans, M.J., additional, Varma, Daya R., additional, Vilanova, Eugenio, additional, Watson, Annetta, additional, Wijeyesakere, Sanjeeva J., additional, Wismer, Tina, additional, Worden, R. Mark, additional, Worek, Franz, additional, Wright, Linzzi K., additional, Yamasue, Hidenori, additional, Yoshida, Takemi, additional, Yoshioka, Toshiharu, additional, Young, Robert A., additional, Zaja-Milatovic, Snjezana, additional, Zinchenko, Valeriy, additional, and Zoltani, Csaba K., additional

Published
2020
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7. Phosgene

Author

Wong, Benjamin, primary, Perkins, Michael W., additional, and Sciuto, Alfred M., additional

Published
2015
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9. List of Contributors

Author

Anadón, Arturo, primary, Anderson, Jaime, additional, Anzai, Jun-ichi, additional, Aschner, Michael, additional, Avdonin, Pavel, additional, Bajgar, Jiri, additional, Bakshi, Kulbir, additional, Balali-Mood, Mahdi, additional, Balszuweit, Frank, additional, Banerjee, Atrayee, additional, Bast, Cheryl B., additional, Bhattacharya, Rahul, additional, Bollinger, Claire E., additional, Casillas, Robert P., additional, Chemtob, Sylvain, additional, Clark, Ryan, additional, Clarkson, Edward D., additional, Cole, Toby B., additional, Coppock, Robert W., additional, Costa, Lucio G., additional, Dettbarn, Wolf-D., additional, Dobbins, Dorothy L., additional, Dorsey, Russell, additional, Dziwenka, Margitta, additional, Emmett, George, additional, Estévez, Jorge, additional, Evans, Timothy J., additional, Fink, John K., additional, Flora, Swaran J.S., additional, Fonnum, Frode, additional, Furlong, Clement E., additional, Fusek, Josef, additional, Gearhart, Jeffery M., additional, Gerecke, Donald R., additional, Glass-Mattie, Dana F., additional, Goel, Saryu, additional, Goncharov, Nikolay, additional, Gordon, Richard K., additional, Gray, Joshua P., additional, Grubic, Zoran, additional, Gulati, Kavita, additional, Gupta, Ramesh C., additional, Gwaltney-Brant, Sharon M., additional, Hamilton, Tracey L., additional, Hauschild, Veronique, additional, Hein, Nichole D., additional, Hilmas, Corey J., additional, Hilmas, Elora, additional, Hood, Darryl B., additional, Jakubowski, Edward M., additional, Jenkins, Richard O., additional, Jett, David A., additional, Jiang, George C-T, additional, Jiao, Yuqin, additional, John, Harald, additional, Johnson, Nathan H., additional, Jokanović, Milan, additional, Jun, Daniel, additional, Kadakkuzha, Beena M., additional, Kassa, Jiri, additional, Katalinic, Maja, additional, Kehe, Kai, additional, Khlebnikova, Natalia, additional, King, Joseph, additional, Kodavanti, Urmila P., additional, Korabecny, Jan, additional, Krishna, Gopala, additional, Krivorotova, Nadezhda, additional, Kuca, Kamil, additional, Kuroiwa, Yukio, additional, Kuznetsov, Anatoliy, additional, Kuznetsov, Sergey, additional, Larsen, Joseph C., additional, Leung, Yiuka, additional, Liu, Jing, additional, Liu, Xin-an, additional, Lockridge, Oksana, additional, Loganathan, Bommanna G., additional, Lugo, Andres M., additional, Maguire, Mark, additional, Makhaeva, Galina F., additional, Malik, Jitendra K., additional, Mars, Tomaz, additional, Martínez-Larrañaga, Maria Rosa, additional, Masson, Patrick, additional, Masunaga, Shigeki, additional, McCallister, Monique, additional, McCauley, Linda A., additional, McNutt, Patrick M., additional, Meek, Edward, additional, Merrill, Elaine, additional, Milanez, Sylvia, additional, Mindukshev, Igor, additional, Mis, Katarina, additional, Mulay, Shree, additional, Murphy, Michael J., additional, Musilek, Kamil, additional, Myhrer, Trond, additional, Okumura, Tetsu, additional, Opresko, Dennis, additional, Orlova, Tatiana, additional, Pål, Aas, additional, Pan, Xiaoping, additional, Patocka, Jiri, additional, Pirkmajer, Sergej, additional, Pita, Rene, additional, Pitt, Jason, additional, Pope, Carey, additional, Prokofieva, Daria, additional, Radilov, Andrey, additional, Ramaiah, Shashi K., additional, Ramesh, Aramandla, additional, Ray, Arunabha, additional, Ray, Kausik, additional, Rembovskiy, Vladimir, additional, Rhoades, Raina, additional, Richardson, Rudy J., additional, Rizzo, Valerio, additional, Robinson, Peter J., additional, Ruark, Chris, additional, Salem, Harry, additional, Satoh, Tetsuo, additional, Savage, Russell E., additional, Savelieva, Elena, additional, Schopfer, Lawrence M., additional, Sciuto, Alfred M., additional, Seto, Yasuo, additional, Shakarjian, Michael P., additional, Sogorb, Miguel, additional, Soreq, Hermona, additional, Sterri, Sigrun Hanne, additional, Stick, Melissa, additional, Suzuki, Kouichiro, additional, Taki, Kenji, additional, Thiermann, Horst, additional, Thompson, Larry J., additional, Uchea, Chibuzor, additional, Ukolov, Anton, additional, Valerio, Luis G., additional, Van der Merwe, Deon, additional, van der Schans, Marcel J., additional, Varma, Daya R., additional, Vilanova, Eugenio, additional, Vinokurov, Maxim, additional, Voitenko, Natalia, additional, Waiskopf, Nir, additional, Watson, Annetta, additional, Wijeyesakere, Sanjeeva J., additional, Wismer, Tina, additional, Woltjer, Randall L., additional, Mark Worden, R., additional, Worek, Franz, additional, Wright, Linnzi, additional, Yeung, David T., additional, Yoshida, Takemi, additional, Young, Robert A., additional, Zaja-Milatovic, Snjezana, additional, Zinchenko, Valeriy, additional, and Zoltani, Csaba K., additional

Published
2015
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10. Transcriptomic Characterization of Inhalation Phosphine Toxicity in Adult Male Sprague–Dawley Rats

Author

Hartog, Matthew A., primary, Lewandowski, Rebecca J., additional, Hofmann, Christopher S., additional, Melber, Ashley A., additional, Rothwell, Cristin C., additional, Sherman, Katherine, additional, Andres, Jaclynn, additional, Tressler, Justin A., additional, Sciuto, Alfred M., additional, Wong, Benjamin, additional, and Hoard-Fruchey, Heidi M., additional

Published
2021
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19. The cardiopulmonary effects of sodium fluoroacetate (1080) in Sprague-Dawley rats

Author

McCranor, Bryan J., primary, Young, Talearia D., additional, Tressler, Justin, additional, Jennings, Laura, additional, Irwin, James, additional, Alli, Nazira A., additional, Abilez, Marilynda K., additional, Stone, Samuel, additional, Racine, Michelle, additional, Devorak, Jennifer L., additional, Sciuto, Alfred M., additional, and Wong, Benjamin, additional

Published
2019
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26. An Official American Thoracic Society Workshop Report: Chemical Inhalational Disasters. Biology of Lung Injury, Development of Novel Therapeutics, and Medical Preparedness

Author

Summerhill, Eleanor M., primary, Hoyle, Gary W., additional, Jordt, Sven-Eric, additional, Jugg, Bronwen J., additional, Martin, James G., additional, Matalon, Sadis, additional, Patterson, Steven E., additional, Prezant, David J., additional, Sciuto, Alfred M., additional, Svendsen, Erik R., additional, White, Carl W., additional, and Veress, Livia A., additional

Published
2017
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33. Conceptual approaches for treatment of phosgene inhalation-induced lung injury

Author

Holmes, Wesley W., primary, Keyser, Brian M., additional, Paradiso, Danielle C., additional, Ray, Radharaman, additional, Andres, Devon K., additional, Benton, Betty J., additional, Rothwell, Cristin C., additional, Hoard-Fruchey, Heidi M., additional, Dillman, James F., additional, Sciuto, Alfred M., additional, and Anderson, Dana R., additional

Published
2016
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37. Evaluation of an in vitro screening model to assess phosgene inhalation injury.

Author

Olivera, Dorian S., Hoard-Fruchey, Heidi, and Sciuto, Alfred M.

Subjects
INHALATION injuries, DRUG development, PHOSGENE, PHOSPHODIESTERASE inhibitors, CELL metabolism, IN vitro studies
Abstract

Therapeutic development against exposure to toxic gases is hindered by the lack of appropriate models to evaluate candidate compounds prior to animal efficacy studies. In this study, anin vitro, air-liquid interface exposure model has been tested to examine its potential application for screening treatments for phosgene (carbonyl chloride)-induced pulmonary injury. Epithelial cultures on Transwell®inserts, combined with a Vitrocell®exposure apparatus, provided a physiologically relevant exposure environment. Differentiated human bronchial epithelial (16HBE) cultures were exposed for 8 min to phosgene ranging from 0 to 64 ppm and assessed for changes in transepithelial electrical resistance (TEER, epithelial barrier integrity), cellular viability (XTT) and post-exposure (PE) cellular metabolic energy status. Exposure to phosgene concentrations ≥8 ppm caused dose-dependent and significant decreases in TEER and XTT which did not recover within 24-h PE. In addition, at 64 ppm the rate of oxidative glutamine metabolism was significantly inhibited at 6 and 24 h after exposure. Glycolytic activities (glucose utilization and lactate production) were also inhibited, but to a lesser extent. Decreased glycolytic function can translate to insufficient energy sources to counteract barrier function failure. Consistent and sensitive markers of phosgene exposure were TEER, cell viability and decreased metabolism. As such, we have assessed an appropriatein vitromodel of phosgene inhalation that produced quantifiable alterations in markers of lung cell metabolism and injury in human airway epithelial cells. Data indicate the suitability of this model for testing classes of anti-edemagenic compounds such as corticosteroids or phosphodiesterase inhibitors for evaluating phosgene therapeutics. [ABSTRACT FROM PUBLISHER]

Published
2017
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39. Development of a Model for Nerve Agent Inhalation in Conscious Rats

Author

ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD, Wong, Benjamin, Perkins, Michael W, Santos, Mariton D, Rodriguez, Ashley M, Murphy, Gleeson, Sciuto, Alfred M, ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD, Wong, Benjamin, Perkins, Michael W, Santos, Mariton D, Rodriguez, Ashley M, Murphy, Gleeson, and Sciuto, Alfred M

Abstract

This study characterizes the development of a head-out inhalation exposure system for assessing respiratory toxicity of vaporized chemical agents in untreated, non-anesthetized rats. The organophosphate diisopropyl fluorophosphate (DFP) induces classical cholinergic toxicity following inhalation exposure and was utilized to validate the effectiveness of this newly designed inhalation exposure system. A saturator cell apparatus was used to generate DFP vapor at 9750, 10950, 12200, 14625 and 19500mg min/m(expn 3) which was carried by filtered nitrogen into a glass mixing tube, where it combined with ambient air before being introduced to the custom-made glass exposure chamber. Male Sprague-Dawley rats (250 300 g) were restrained in individual head-out plethysmography chambers, which acquired respiratory parameters before, during and after agent exposure. All animals were acclimated to the exposure system prior to exposure to reduce novel environment-induced stress. The LCt50, as determined by probit analysis, was 12 014mg min/m3. Weight loss in exposed animals was dose-dependent and ranged from 8 to 28% of their body weight 24 h after exposure. Increased salivation, lacrimation, urination, defecation (SLUD) and mild muscular fasciculation were observed in all DFP-exposed animals during and immediately following exposure. In all exposed animals, DFP vapor produced significant inhibition of acetylcholinesterase (AChE) activity in cardiac blood, bronchoalveolar lavage fluid (BALF), whole brain and lung tissue as well as alterations in tidal volume and minute volume. These studies have provided valuable information leading to the initiation of studies evaluating inhalational toxicity and treatments following exposure to the more lethal and potent chemical warfare nerve agents., The original document contains color images. Published in Toxicology Mechanisms and Methods, v23 n7 p537-547, 2013.

Published
2013

40. Determination of LCt50s in Anesthetized Rats Exposed to Aerosolized Nerve Agents

Author

ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD, Collins, Jennifer L, Peng, Xinqi, Lee, Robyn, Witriol, Alicia, Pierre, Zdenka, Sciuto, Alfred M, ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD, Collins, Jennifer L, Peng, Xinqi, Lee, Robyn, Witriol, Alicia, Pierre, Zdenka, and Sciuto, Alfred M

Abstract

Nerve agents pose a threat to the respiratory tract with exposure that could result in acute compromised lung performance and death. The determination of toxicity by inhalation is important for the rational development of timely therapeutic countermeasures. This study was designed to deliver aerosolized dilute nerve agents in a dose-response manner to investigate the extent of lethality of nerve agents: soman, sarin, VX and VR. Male rats (240-270 g) were anesthetized intramuscularly with 10 mg/kg xylazine and 90 mg/kg ketamine. Following anesthesia, rats were intubated with a glass endotracheal tube (ET) and placed in a glove box. The ET was connected to a closed circuit nebulizer system (Aeroneb, Aerogen, Inc.) that delivered a particle size of 2.0 micro m and was in series between the ventilator and the ET. Nerve agents were delivered by a small animal ventilator set for a volume of 2.5 ml x 60-80 breaths/min. VX or VR were nebulized and delivered in concentrations ranging from 6.25-800 micro g/kg over a 10-min exposure time period. Sarin (GB) or soman (GD), 6.5-1250 micro g/kg, were delivered in a similar manner. Lethality by inhalation occurred either during the 1 0-min exposure period or less than 15 min after the cessation of exposure. Survivors were euthanized at 24 h postexposure. LCt50 estimates ( 95% confidence intervals [Cis]) were obtained from the sequential stage-wise experiments using the probit analysis. Probit analysis revealed that the LD50 for VX was 110.7 micro g/kg (CI: 73.5-166.7), VR 64.2 micro g/kg (CI: 42.1-97.8); soman (GD), 1 67 micro g/kg (CI: 90-31 0), and sarin (GB), 154 micro g/ kg (CI: 98-242), respectively. Although VR is a structural isomer of VX, the compounds appear to be markedly different in terms of toxicity when delivered by aerosol., The original document contains color images. Prepared in collaboration with 27 SOCES/CEAN Cannon Air Force Base, NM. Published in Toxicology Mechanisms and Methods, v23 n2 p127-133, 2013.

Published
2013

42. Gas Chromatographic-Mass Spectrometric Analysis of Sulfur Mustard-Plasma Protein Adducts: Validation and Use in a Rat Inhalation Model

Author

ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD, Capacio, Benedict R., Smith, J. R., Lawrence, Richard J., Boyd, Brian L., Witriol, Alicia M., Conti, Michele L., Collins, Jennifer L., Sciuto, Alfred M., ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD, Capacio, Benedict R., Smith, J. R., Lawrence, Richard J., Boyd, Brian L., Witriol, Alicia M., Conti, Michele L., Collins, Jennifer L., and Sciuto, Alfred M.

Abstract

Sulfur mustard (HD) is an alkylating agent that reacts rapidly with macromolecular targets resulting in the formation of stable adducts providing depots for markers of exposure. The purpose of this study was to validate an analytical procedure for detection of HD-plasma protein adducts and to establish the utility of the method in an HD rat inhalation study. Calibration curves were prepared in human and rat plasma at six levels of HD (12.5 to 400nM). Correlation coefficients for the mean data were 0.9987 for human and 0.9992 for rat plasma. The percent coefficient of variation (%CV) derived from the mean concentration data ranged from 0.53 to 14.1% in human (n = 5) and 0.57 to 10.63% in rat (n = 6) plasma. Intraday and interday precision and accuracy studies were conducted at three concentration levels (25, 150, 300nM) to represent low, medium, and high concentrations of HD relative to those employed in the calibration curve. Precision and accuracy were assessed by determining %CV and %error, respectively. For intra- and interday studies, the %CVs and absolute % errors were less than 15%. The limits of quantitation were 20.88nM for human and 16.73nM for rat plasma. In animal studies, rats received nebulized HD at six doses. The data indicate a dose-dependent relationship between maximal plasma concentrations and dose administered (R(2) =0.9728). Results from this study indicate an accurate, precise, and sensitive method. The method was useful in determining plasma protein adduct formation in a rat inhalation model., Pub. in Journal of Analytical Toxicology, v32 p37-43, 2008. Supported in part by Defense Threat Reduction Agency.

Published
2008

44. Vapor inhalation exposure to soman in conscious untreated rats: preliminary assessment of neurotoxicity.

Author

Perkins, Michael W., Wong, Benjamin, Rodriguez, Ashley, Devorak, Jennifer L., Dao, Thuy T., Leuschner, Jessica A., Kan, Robert K., and Sciuto, Alfred M.

Subjects
NEUROTOXICOLOGY, SOMAN, NERVE gases, CHEMICAL warfare agents, CHOLINESTERASES
Abstract

Neurological toxicity and brain injury following vapor inhalation exposure to the chemical warfare nerve agent (CWNA) soman (GD) were examined in untreated non-anesthetized rats. In this study, male Sprague-Dawley rats (300–350 g) were exposed to 600 mg × min/m3of soman or vehicle in a customized head-out inhalation system for 7 min. Convulsant animals were observed for clinical signs and various regions of the brain (dorsolateral thalamus, basolateral amygdala, piriform cortex, and lateral cortex) were collected for pathological observations 24 h post-exposure. Signs of CWNA-induced cholinergic crises including salivation, lacrimation, increased urination and defecation, and tremors were observed in all soman-exposed animals. Soman-exposed animals at 24 h post-exposure lost 11% of their body weight in comparison to 2% in vehicle-exposed animals. Whole blood acetylcholinesterase (AChE) activity was significantly inhibited in all soman-exposed groups in comparison to controls. Brain injury was confirmed by the neurological assessment of hematoxylin-eosin (H&E) staining and microscopy in the piriform cortex, dorsolateral thalamus, basolateral amygdala, and lateral cortex. Severe damage including prominent lesions, edematous, congested, and/or hemorrhagic tissues was observed in the piriform cortex, dorsolateral thalamus, and lateral cortex in soman-exposed animals 24 h post-exposure, while only minimal damage was observed in the basolateral amygdala. These results indicate that inhalation exposure to soman vapor causes neurological toxicity and brain injury in untreated unanesthetized rats. This study demonstrates the ability of the described soman vapor inhalation exposure model to cause neurological damage 24 h post-exposure in rats. [ABSTRACT FROM PUBLISHER]

Published
2016
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49. Oxidative Stress May Contribute To The Obstructive Pulmonary Dysfunction From Inhalation Exposure To Nerve Agent VX In Rats

Author

Peng, Xinqi, primary, Rodriguez, Ashley M., additional, Witriol, Alicia M., additional, Bowens, Christopher M., additional, Simons, Jannitt B., additional, Benjamin, Brittany M., additional, Nordmark, Brittany A., additional, Collins, Jennifer L., additional, Hamilton, Tracey A., additional, Kan, Robert K., additional, and Sciuto, Alfred M., additional

Published
2011
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