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Toxicol Mech Methods 2020 Mar 30:1-16. Epub 2020 Mar 30.

Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.

The elemental halogens include chlorine, bromine, and phosgene. Halogen gas can be directly weaponized and employed in warfare or terrorism. Industrial stockpiles or halogen transport can provide targets for terrorist attack as well as an origin for accidental release creating a risk for potential mass-casualty incidents. Read More

Toxicol Lett 2020 May 23;323:10-18. Epub 2020 Jan 23.

Faculty of Health Science, School of Pharmacy/Toxicology, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.

Chloropicrin is a volatile and reactive chemical that has been utilized as a warfare agent and a pesticide to fumigate soil against insects, fungi and nematodes. It poses a health risk to humans and animals if inhaled. The main source of chloropicrin exposure is occupational and occurs during its manufacture, transport and fumigation. Read More

Biomed Pharmacother 2020 Jan 8;121:109603. Epub 2019 Nov 8.

Department of Intensive Care Unit, Center of Emergency & Intensive Care Unit, Jinshan Hospital, Fudan University, Shanghai, China; Department of Intensive Care Unit, Medical Research Center of Chemical Injury, Jinshan Hospital, Fudan University, Shanghai, China; Department of Intensive Care Unit, Medical Center of Radiation Injury, Jinshan Hospital, Fudan University, Shanghai, China. Electronic address:

Accidental phosgene exposure can result in acute lung injury (ALI). Mesenchymal stem cells (MSCs) have been found to alleviate phosgene-induced ALI. However, the mechanism of MSCs underlying such protective effect remains largely unexplored. Read More

Toxicol Lett 2019 Nov 6;316:94-108. Epub 2019 Sep 6.

Hanover Medical School, Hannover, Germany; Bayer HealthCare, Wuppertal, Germany (retired). Electronic address:

The toxic effects resulting from inhalation exposure depend on both the concentration (C) of the inhaled substance and the exposure duration (t), including the assumptions that the exposure-limiting toxic effect is linearly linked with the accumulated C × t (inhaled dose), and detoxification or compensatory responses diminishing this dose are negligible. This interrelationship applies for both constant and fluctuating concentrations and is usually expressed by the toxic load equation C × t = constant effect (k). The toxic load exponent 'n' is derived from both C- and t-dependent exponents with C×t = k with n = b/b. Read More

Toxicol Mech Methods 2019 Oct 16;29(8):604-615. Epub 2019 Jul 16.

Rubicon Biotechnology , Anaheim , CA , USA.

Phosgene is classified as a chemical warfare agent, yet data on its short-duration high concentration toxicity in a nose-only exposure rat model is sparse and inconsistent. Hence, an exposure system for short-term/high concentration exposure was developed and characterized. Herein, we report the median lethal concentration (LC) for a 10-min nasal exposure of phosgene in a 24-h rat survival model. Read More

Inhal Toxicol 2019 02 9;31(2):52-60. Epub 2019 May 9.

a Department of Intensive Care Unit, Center of Emergency & Intensive Care Unit, Jinshan Hospital , Fudan University , Shanghai , China.

We have previously found that mesenchymal stem cell (MSC) therapy can ameliorate phosgene-induced acute lung injury (ALI). Moreover, exosomes can be used as a cell-free alternative therapy. In the present study, we aimed to assess the effect of MSC-derived exosomes on phosgene-induced ALI. Read More

Toxicol Lett 2019 Sep 30;312:204-213. Epub 2019 Apr 30.

Department of Anesthesiology and Perioperative Medicine, Birmingham, AL, 35205-3703, United States; Division of Molecular and Translational Biomedicine, Birmingham, AL, 35205-3703, United States; Pulmonary Injury and Repair Center, Birmingham, AL, 35205-3703, United States; Center for Free Radical Biology, Birmingham, AL, 35205-3703, United States; University of South Alabama Health College of Medicine, Mobile, AL, United States; St. Louis University, St. Louis, MO, 63104, United States. Electronic address:

Phosgene (Carbonyl Chloride, COCl) remains an important chemical intermediate in many industrial processes such as combustion of chlorinated hydrocarbons and synthesis of solvents (degreasers, cleaners). It is a sweet smelling gas, and therefore does not prompt escape by the victim upon exposure. Supplemental oxygen and ventilation are the only available management strategies. Read More

Toxicol Lett 2019 May 19;305:32-39. Epub 2019 Jan 19.

Department of Toxicology, Fourth Military Medical University, China; Covestro Deutschland AG, Global Phosgene Steering Group, Leverkusen, Germany; Hanover Medical School, Hannover, Germany. Electronic address:

Phosgene-induced acute lung injury (ALI) is characterized by a concentration x time (Cxt)-dependent increased pulmonary vascular permeability, phenotypically manifested as potentially life-threatening acute lung edema. In contemporary animal bioassays, the quantification of protein in bronchoalveolar lavage fluid (BAL) is taken as an unequivocal endpoint suggestive of disruption of alveolar barrier function. However, extravasated protein can only be a surrogate endpoint for assessing the extravascular fluid dynamics of the lung. Read More

J R Army Med Corps 2019 Jun 23;165(3):183-187. Epub 2018 Oct 23.

Southampton Centre for Biomedical Research, University of Southampton, Southampton, UK

World War 1 ended 100 years ago. The aftermath included the consolidation of significant advances in medical care of casualties. Some of these advances were made in the care of chemical casualties, in particular the mechanisms of toxicity and treatment of phosgene exposure. Read More

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 2018 Aug;36(8):573-579

Emergency & Intensive Care Centre of Jinshan Hospital affiliated to Fudan University, Medical Research Centre for Chemical Injury, Emergency and Critical Care of Fudan University, Shanghai 201508, China.

To investigate the effects of methylprednisolone on NOD-like receptor hot protein domain-associated protein 3 (NLRP3) inflammasome in phosgene-induced acute lung injury. Rats were randomly divided into four groups, 10 rats in Air group (inhalation of air of the same volume as the phosgene group) , 10 rats in Phosgene group (inhalation of 8.33 mg/L with 100% purity phosgene for 5 min) , 10 rats in Saline control group (inhalation of the same dose of phosgene and 2 mg/kg saline via tail vein injection one hour later) , 10 rats in MP group (inhalation of the same dose of phosgene and 2 mg/kg MP via tail vein injection one hour later) . Read More

Inhal Toxicol 2018 Mar - Apr;30(4-5):187-194

a Center of Emergency & Intensive Care Unit, Jinshan Hospital , Fudan University , Shanghai , China.

Objective: Angiopoietin-1 (Ang1) is reported to have the ability to attenuate endothelial permeability and inflammation during the stress condition and is considered to play a critical role in vascular stabilization. The aim of this study was to investigate the mechanisms involved in the protective effects of adenovirus-delivered Ang1 in phosgene-induced acute lung injury (ALI).

Methods: ALI was induced in rats by phosgene exposure at 8. Read More

Toxicol Lett 2018 Jun 21;290:145-152. Epub 2018 Mar 21.

CBR Division, Dstl Porton Down, Salisbury SP4 OJQ, Wiltshire, UK. Electronic address:

The toxic industrial chemical (TIC) phosgene remains an important chemical intermediate in many industrial processes. Inhalation of phosgene can cause an acute lung injury (ALI) which, in severe cases may result in death. There are currently no effective pharmacological therapies or evidence-based treatment guidelines for managing exposed individuals. Read More

ACS Sens 2018 01 26;3(1):27-43. Epub 2017 Dec 26.

Department of Chemistry and Nano Science, Ewha Womans University , Seoul, 120-750, Korea.

The extreme toxicity and ready accessibility of nerve agents and phosgene has caused an increase in the demand to develop effective systems for the detection of these substances. Among the traditional platforms utilized for this purpose, chemosensors including surface acoustic wave (SAW) sensors, enzymes, carbon nanotubes, nanoparticles, and chromophore based sensors have attracted increasing attention. In this review, we describe in a comprehensive manner recent progress that has been made on the development of chromophore-based chemosensors for detecting nerve agents (mimic) and phosgene. Read More

Toxicol Lett 2018 Sep 12;293:112-119. Epub 2017 Nov 12.

Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address:

Phosgene Oxime (CX, ClCNOH), a halogenated oxime, is a potent chemical weapon that causes immediate acute injury and systemic effects. CX, grouped together with vesicating agents, is an urticant or nettle agent with highly volatile, reactive, corrosive, and irritating vapor, and has considerably different chemical properties and toxicity compared to other vesicants. CX is absorbed quickly through clothing with faster cutaneous penetration compared to other vesicating agents causing instantaneous and severe damage. Read More

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 2017 Jul;35(7):491-496

Emergency & Intensive Care Centre for Chemical Accident of Jinshan Hospital affiliated to Fudan University, Shanghai 201508, China.

To investigate changes of NLRP3 signal transduction pathway of acute lung injury induced by phosgene to analyze NLRP3-mediated IL-1β release inflammatory process in rats. Rats were randomly divided into two groups, 10 rats in the Air group that consists of the rats with air exposure, 10 rats in the Psg group that consists of the rats with phosgene exposure at 8.33 g/m(3) for 5 min. Read More

Toxics 2017 Sep 21;5(4). Epub 2017 Sep 21.

Graduate Institute of Bioresources, National Pingtung University of Science and Technology, Pingtung 912, Taiwan.

Among the halogenated hydrocarbons, chloromethanes (i.e., methyl chloride, CH₃Cl; methylene chloride, CH₂Cl₂; chloroform, CHCl₃; and carbon tetrachloride, CCl₄) play a vital role due to their extensive uses as solvents and chemical intermediates. Read More

Ann Agric Environ Med 2017 Sep 11;24(3):406-410. Epub 2017 May 11.

Department of Pathomorphology, Poznan University of Medical Sciences.

Introduction And Objective: Firefighters are considered a healthy and fit group of individuals, well-prepared for taking action in disaster situations. While working, they suffer from exposure to certain toxic agents, especially combustion products generated when a fire takes place. Among them, the most frequent and the most toxic are: carbon monoxide, hydrogen cyanide, ammonia, and those resulting from PVC combustion - hydrochloride, phosgene and chloride. Read More

Toxicol Appl Pharmacol 2017 02 11;317:25-32. Epub 2017 Jan 11.

Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

Phosgene Oxime (CX), an urticant or nettle agent categorized as a vesicant, is a potential chemical warfare and terrorist weapon. Its exposure can result in widespread and devastating effects including high mortality due to its fast penetration and ability to cause immediate severe cutaneous injury. It is one of the least studied chemical warfare agents with no effective therapy available. Read More

Toxicol Mech Methods 2017 Jan 28;27(1):45-51. Epub 2016 Oct 28.

a Analytical Toxicology Division, U.S. Army Medical Research Institute of Chemical Defense , Aberdeen Proving Ground, MD , USA.

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, an in 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. Read More

Inhal Toxicol 2016 10 19;28(12):572-579. Epub 2016 Sep 19.

a Department of Intensive Care Unit , Center of Emergency & Intensive Care Unit, Jinshan Hospital, Fudan University , Shanghai , China.

An increase in epithelial cell permeability has been proposed to contribute to phosgene-induced acute lung injury (ALI). However, no specific and effective means for blocking increases in permeability are currently available. Cell-based therapy using bone marrow-derived mesenchymal stem cells (MSCs) is an attractive new approach. Read More

Anaesth Intensive Care 2016 07;44 Suppl:24-30

Senior Anaesthetist, Westmead Hospital, Westmead, NSW.

The Great War began just over a century ago and this monumental event changed the world forever. 1915 saw the emergence of gas warfare-the first weapon of mass terror. It is relevant to anaesthetists to reflect on these gases for a number of reasons. Read More

Sci Total Environ 2016 Dec 9;573:1287-1293. Epub 2016 Jul 9.

Aix Marseille Univ, CNRS, LCE, Marseille, France. Electronic address:

The heterogeneous reactions of gas-phase ozone and two pyrethroid pesticides, deltamethrin and permethrin, which are the most frequently applied insecticides today, has been investigated. Tentative identifications of heterogeneous ozonolysis products of both pesticides reveal that the reaction mechanisms differ and are mainly influenced by the presence of the cyano moiety at the α-position of deltamethrin (pyrethroid type II). The mechanism study also suggests the important role of water. Read More

Profiles Drug Subst Excip Relat Methodol 2016 31;41:133-321. Epub 2015 Dec 31.

King Saud University, Riyadh, Saudi Arabia.

This chapter includes the aspects of carbamazepine. The drug is synthesized by the use of 5H-dibenz[b,f]azepine and phosgene followed by subsequent reaction with ammonia. Carbamazepine is generally used for the treatment of seizure disorders and neuropathic pain, it is also important as off-label for a second-line treatment for bipolar disorder and in combination with an antipsychotic in some cases of schizophrenia when treatment with a conventional antipsychotic alone has failed. Read More

Sci Rep 2016 Feb 24;6:22023. Epub 2016 Feb 24.

Charles Perkins Centre, University of Sydney, Sydney, Australia.

Biomarkers have gained immense scientific interest and clinical value in the practice of medicine. With unprecedented advances in high-throughput technologies, research interest in identifying novel and customized disease biomarkers for early detection, diagnosis, or drug responses is rapidly growing. Biomarkers can be identified in different levels of molecular biomarkers, networks biomarkers and dynamical network biomarkers (DNBs). Read More

Clin Toxicol (Phila) 2016 22;54(2):79-91. Epub 2015 Dec 22.

a Department of Emergency Medicine , Drexel University College of Medicine , Philadelphia , PA , USA.

Introduction: Chemical weapons dumped into the ocean for disposal in the twentieth century pose a continuing environmental and human health risk.

Objective: In this review we discuss locations, quantity, and types of sea-dumped chemical weapons, related environmental concerns, and human encounters with sea-dumped chemical weapons.

Methods: We utilized the Ovid (http://ovidsp. Read More

Inhal Toxicol 2015 ;27(14):832-40

a Biomedical Research Center, Battelle - LSR , Columbus , OH , USA and.

Context: Phosgene's primary mode of action is as a pulmonary irritant characterized by its early latent phase where life-threatening, non-cardiogenic pulmonary edema is typically observed 6-24 h post-exposure.

Objective: To develop an inhaled phosgene acute lung injury (ALI) model in C57BL/6 mice that can be used to screen potential medical countermeasures.

Methods: A Cannon style nose-only inhalation exposure tower was used to expose mice to phosgene (8 ppm) or air (sham). Read More

Toxicol Lett 2016 Feb 10;244:8-20. Epub 2015 Nov 10.

Analytical Toxicology Division, US Army Medical Research Institute of Chemical Defense, 2900 Ricketts Point Road, Aberdeen Proving Ground, MD 21010-5400, United States. Electronic address:

Toxic industrial chemicals are used throughout the world to produce everyday products such as household and commercial cleaners, disinfectants, pesticides, pharmaceuticals, plastics, paper, and fertilizers. These chemicals are produced, stored, and transported in large quantities, which poses a threat to the local civilian population in cases of accidental or intentional release. Several of these chemicals have no known medical countermeasures for their toxic effects. Read More

Toxicol Lett 2016 Feb 10;244:21-27. Epub 2015 Nov 10.

Research Division, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5400, USA. Electronic address:

Phosgene (CG), a toxic inhalation and industrial hazard, causes bronchoconstriction, vasoconstriction and associated pathological effects that could be life threatening. Ion channels of the transient receptor potential (TRP) family have been identified to act as specific chemosensory molecules in the respiratory tract in the detection, control of adaptive responses and initiation of detrimental signaling cascades upon exposure to various toxic inhalation hazards (TIH); their activation due to TIH exposure may result in broncho- and vasoconstriction. We studied changes in the regulation of intracellular free Ca(2+) concentration ([Ca(2+)]i) in cultures of human bronchial smooth muscle cells (BSMC) and human pulmonary microvascular endothelial cells (HPMEC) exposed to CG (16ppm, 8min), using an air/liquid interface exposure system. Read More

Inhal Toxicol 2015 13;27(5):254-61. Epub 2015 May 13.

Center of Emergency & Intensive Care Unit, Jinshan Hospital, Fudan University , Shanghai , China .

Accidental phosgene exposure could result in acute lung injury (ALI), effective therapy is needed for the patients with phosgene-induced ALI. As a type of cells with therapeutic potential, mesenchymal stem cells (MSCs) have been showed its efficacy in multiple diseases. Here, we assessed the therapeutic potential of MSCs in phosgene-induced ALI and explored the related mechanisms. Read More

Toxicol Sci 2015 Jul 13;146(1):89-100. Epub 2015 Apr 13.

*Environmental Respiratory Health and Chemistry and Inhalation Exposure Programs, Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108 and Department of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115

Phosgene exposure via an industrial or warfare release produces severe acute lung injury (ALI) with high mortality, characterized by massive pulmonary edema, disruption of epithelial tight junctions, surfactant dysfunction, and oxidative stress. There are no targeted treatments for phosgene-induced ALI. Previous studies demonstrated that nitric oxide synthase 2 (NOS-2) is upregulated in the lungs after phosgene exposure; however, the role of NOS-2 in the pathogenesis of phosgene-induced ALI remains unknown. Read More

Chem Soc Rev 2015 May 20;44(10):3079-116. Epub 2015 Mar 20.

Key Laboratory for Green Chemical Technology of Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.

Dialkyl carbonates are important organic compounds and chemical intermediates with the label of "green chemicals" due to their moderate toxicity, biodegradability for human health and environment. Indeed, owing to their unique physicochemical properties and versatility as reagents, a variety of phosgene-free processes derived from CO or CO2 have been explored for the synthesis of dialkyl carbonates. In this critical review, we highlight the recent achievements (since 1997) in the synthesis of dialkyl carbonates based on CO and CO2 utilization, particularly focusing on the catalyst design and fabrication, structure-function relationship, catalytic mechanisms and process intensification. Read More

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 2014 Nov;32(11):813-8

Emergency & Intensive Care Centre for Chemical Accident of Jinshan Hospital Affiliated to Fudan University, Shanghai 201508, China. E-mail:

Objective: To investigate the dynamic changes of a group of cytokines in phosgene-induced lung injury and the function of different dose of ulinastatin through animal experiment.

Methods: 104 male SD rats were randomly assigned into the control group, ulinastatin control group, phosgene treatment groups and different dose of ulinastatin intervention groups, 8 rats each group. Treatment groups were dynamic constant exposure in phosgene, and immediately injected ulinastatin intraperitoneal, and then the experimental animal, the lung tissue biopsy, lung wet/dry ratio, RT-PCR detection, the plasma for detection of Bio-Plex 18 cytokines. Read More

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 2014 Sep;32(9):653-9

Emergency & Intensive Care Centre for Chemical Accident of Jinshan Hospital affiliated to Fudan University, Shanghai 201508, China.

Objective: To investigate the effects of adenovirus-delivered angiopoietin-1 siRNA (Ad. Ang-1siRNA) on the expression of matrix metalloproteinase-2, 9 (MMP-2, 9) and tissue inhibitor of metallopro-teinase-1 (TIMP-1) in rats with acute lung injury (ALI) induced by phosgene (Psg).

Methods: We first established a rat model of Psg-induced acute lung injury (ALI). Read More

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 2014 Sep;32(9):648-52

Emergency & Intensive Care Center for Chemical Accident of Jinshan Hospital Affiliated to Fudan University, Shanghai 201508, China. E-mail:

Objective: To investigate the effect of melatonin (MT) on p38 mitogen-activated protein kinase (MAPK) signaling pathway in rats with phosgene-induced lung injury.

Methods: Fifty specific pathogen-free male Sprague-Dawley rats were randomly divided into phosgene inhalation group, air control group, saline control group, MT treatment group, and SB203580 (specific inhibitor of p38 MAPK) group, with 10 mice in each group. All groups except the air control group were exposed to phosgene, and the animals were sacrificed 6 h later. Read More

Exp Toxicol Pathol 2015 Feb 15;67(2):109-16. Epub 2014 Nov 15.

Bayer HealthCare Pharma, Experimental Toxicology, Wuppertal, Germany. Electronic address:

Various therapeutic regimes have been proposed for treatment of phosgene-induced acute lung injury (P-ALI). Most of these treatments rely on late-stage supportive measures to maintain the oxygenation of the lung. This exploratory proof-of-concept study on Beagle dogs focused on protective positive end-expiratory pressure (PEEP) ventilation, initiated early at the yet asymptomatic stage after phosgene exposure. Read More

Toxicology 2014 Dec 22;326:109-18. Epub 2014 Oct 22.

Department of Toxicology, Bayer Pharma AG, Wuppertal 42096, Germany; Hannover Medical School, Hannover, Germany. Electronic address:

This study compares changes in cardiopulmonary function, selected endpoints in exhaled breath, blood, and bronchoalveolar lavage fluid (BAL) following a single, high-level 30-min nose-only exposure of rats to chlorine and phosgene gas. The time-course of lung injury was systematically examined up to 1-day post-exposure with the objective to identify early diagnostic biomarkers suitable to guide countermeasures to accidental exposures. Chlorine, due to its water solubility, penetrates the lung concentration-dependently whereas the poorly water-soluble phosgene reaches the alveolar region without any appreciable extent of airway injury. Read More

Toxicol Lett 2014 Aug 6;229(1):85-92. Epub 2014 Jun 6.

Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing Hospital, Ministry of Health, Beijing 100730, China. Electronic address:

Various therapeutic regimes have been proposed with limited success for treatment of phosgene-induced acute lung injury (P-ALI). Corticoids were shown to be efficacious against chlorine-induced lung injury but there is still controversy whether this applies also to P-ALI. This study investigates whether different regimen of curatively administered budesonide (BUD, 10 mg/kg bw, i. Read More

Inhal Toxicol 2014 Feb;26(3):185-92

Center of Emergency & Intensive Care Unit .

Animals exposed to phosgene (Psg) result in acute lung injury (ALI). We have recently reported that angiopoietin-1 (Ang1) reduces inflammation and vascular hyperpermeability in ALI animals. In this study, we examined whether the beneficial effects of adenovirus-delivered Ang1 (Ad/Ang1) on inflammatory responses in Psg-induced ALI rats are due to the suppression of the nuclear factor-kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) pathways, which play crucial roles in inflammatory responses in ALI. Read More

Toxicology 2014 Jan 23;315:17-23. Epub 2013 Nov 23.

Beijing Institute of Respiratory Medicine, Beijing Hospital, Ministry of Health, Beijing 100730, China. Electronic address:

Life-threatening acute lung injury potentially occurs following high-level accidental exposures to phosgene gas. This situation was mirrored in rats exposed nose-only at 900-1000 mg phosgene/m(3)min. At this exposure level, previous studies on rats demonstrated sustained reflexively induced cardiopulmonary dysfunction and evidence of vascular fluid redistribution. Read More

J Med Toxicol 2014 Mar;10(1):51-6

Division of Medical Toxicology, Department of Emergency Medicine, University of Virginia School of Medicine, PO Box 800774, Charlottesville, VA, 22908-0774, USA,

Introduction: Phosgene is a rare exposure with strong clinical implications. We report a phosgene exposure that resulted in the patient's death.

Case Report: A 58 year-old man arrived to the emergency department 1 hour after exposure to phosgene with complaints of a sore throat. Read More

Toxicology 2013 Aug 14;310:104-14. Epub 2013 Jun 14.

Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing 100069, China.

Exhaled nitric oxide (eNO) has received increased attention in clinical settings because this technique is easy to use with instant readout. However, despite the simplicity of eNO in humans, this endpoint has not frequently been used in experimental rat models of septic (endotoxemia) or irritant acute lung injury (ALI). The focus of this study is to adapt this method to rats for studying ALI-related lung disease and whether it can serve as instant, non-invasive biomarker of ALI to study lung toxicity and pharmacological efficacy. Read More

Drug Metab Lett 2012 ;6(4):221-34

Department of Medicinal Chemistry, Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, (NIPER), Sector-67, S. A. S. Nagar - 160 062, Punjab, India.

Chloroform and Halothane are well known hepatotoxic anesthetics for which toxicity is attributed to their reactive metabolites. The molecular level details of reactions leading to the formation of reactive metabolites from chloroform and halothane have not been explored. Potential energy surface (PES) for the formation of phosgene (a toxic intermediate) from Chloroform has been studied using quantum chemical methods. Read More

Inhal Toxicol 2013 Apr;25(5):272-9

Center of Emergency & Intensive Care Unit, Jinshan Hospital, Fudan University, 1508 Longhang Road, Shanghai 201508, P.R. China.

Context: Exposure to phosgene can result in an acute lung injury, leading to pulmonary edema and even death. Angiopoietin-1 (Ang1) is a critical factor for vascular stabilization due to its ability to reduce endothelial permeability and inflammation.

Objective: In this study, the histopathological changes of the lungs after exposure to phosgene and the effect of Ang1 treatment were examined. Read More

BMC Neurosci 2013 Apr 18;14:49. Epub 2013 Apr 18.

Research Division, US Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving Ground, Maryland, 21010-5400, USA.

Background: Immortalized neuronal cell lines can be induced to differentiate into more mature neurons by adding specific compounds or growth factors to the culture medium. This property makes neuronal cell lines attractive as in vitro cell models to study neuronal functions and neurotoxicity. The clonal human neuroblastoma BE(2)-M17 cell line is known to differentiate into a more prominent neuronal cell type by treatment with trans-retinoic acid. Read More

Am J Respir Cell Mol Biol 2013 Sep;49(3):368-83

Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, PA 15219, USA.

In this study, a genetically diverse panel of 43 mouse strains was exposed to phosgene and genome-wide association mapping performed using a high-density single nucleotide polymorphism (SNP) assembly. Transcriptomic analysis was also used to improve the genetic resolution in the identification of genetic determinants of phosgene-induced acute lung injury (ALI). We prioritized the identified genes based on whether the encoded protein was previously associated with lung injury or contained a nonsynonymous SNP within a functional domain. Read More

Nucl Med Biol 2013 Jul 11;40(5):651-7. Epub 2013 Apr 11.

Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan.

Introduction: Irinotecan is a semisynthetic derivative of camptothecin that exerts potent antitumor activity by inhibiting topoisomerase I. Despite much research into the complex pharmacokinetic profile and pharmacodynamic effects of irinotecan, unpredictable and severe side effects are still commonly observed. In this study, we synthesized [(11)C]irinotecan as a positron emission tomography (PET) probe, performed the metabolite analysis, and evaluated the biodistribution and kinetics of [(11)C]irinotecan using small animal PET. Read More

Rev Physiol Biochem Pharmacol 2013 ;165:31-65

Rudolf Boehm-Institut für Pharmakologie und Toxikologie, Selbständige Abteilung für Klinische Pharmakologie, Universität Leipzig, Härtelstr. 16-18, Leipzig, 04107, Germany.

Acute toxic lung injury by reactive inhalational compounds is an important and still unresolved medical problem. Hazardous gases or vapors, e. g. Read More

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 2012 Nov;30(11):834-8

Emergency & Intensive Care Center for Chemical Accident of Jinshan Hospital Affiliated to Fudan University, Shanghai 201508, China.

Objective: To investigate the antioxidant effect of melatonin (MT) in the rats with phosgene-induced lung injury and its possible mechanism.

Methods: Fifty male SD rats were equally randomized into phosgene exposure group, air control group, MT treatment group, dexamethasone (DX) treatment group, and negative control group. All groups except the air control group were exposed to 8. Read More

Sci Rep 2012 10;2:813. Epub 2012 Dec 10.

Collaborative Research Center for Innovative Mathematical Modelling, Institute of Industrial Science, University of Tokyo , Tokyo 153-8505, Japan.

Identifying a critical transition and its leading biomolecular network during the initiation and progression of a complex disease is a challenging task, but holds the key to early diagnosis and further elucidation of the essential mechanisms of disease deterioration at the network level. In this study, we developed a novel computational method for identifying early-warning signals of the critical transition and its leading network during a disease progression, based on high-throughput data using a small number of samples. The leading network makes the first move from the normal state toward the disease state during a transition, and thus is causally related with disease-driving genes or networks. Read More

Toxicol Sci 2013 Feb 9;131(2):612-28. Epub 2012 Nov 9.

Department of Toxicology, Fourth Military Medical University, Xi'an, 710032, China.

Phosgene gas is a lower respiratory tract irritant. As such, it stimulates nociceptive vagal C-fiber-related reflexes in a dose-rate and concentration × exposure duration (C × t)-dependent manner. In rats, this reflex is characterized by extended apnea time periods, bradycardia, and hypothermia. Read More