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Toxicology Mechanisms and Methods May 2021Highly toxic industrial chemicals that are widely accessible, and hazardous chemicals like phosgene oxime (CX) that can be easily synthesized, pose a serious threat as... (Review)
Review
Highly toxic industrial chemicals that are widely accessible, and hazardous chemicals like phosgene oxime (CX) that can be easily synthesized, pose a serious threat as potential chemical weapons. In addition, their accidental release can lead to chemical emergencies and mass casualties. CX, an urticant, or nettle agent, grouped with vesicating agents, causes instant pain, injury and systemic effects, which can lead to mortality. With faster cutaneous penetration, corrosive properties, and more potent toxicity compared to other vesicating agents, CX causes instantaneous and severe tissue damage. CX, a potential chemical terrorism threat agent, could therefore be weaponized with other chemical warfare agents to enhance their harmful effects. CX is the least studied vesicant and its acute and long-term toxic effects as well as its mechanism of action are largely unknown. This has hampered the identification of therapeutic targets and the development of effective medical countermeasures. There are only protective measures, decontamination, and supportive treatments available for reducing the toxic effects from CX exposure. This review summarizes CX toxicity, its known mechanism of action, and our current studies exploring the role of mast cell activation and associated signaling pathways in CX cutaneous exposure under the National Institutes of Health Countermeasures Against Chemical Threats program. Potential treatment options and the development of effective targeted countermeasures against CX-induced morbidity and mortality is also discussed.
Topics: Chemical Warfare Agents; Irritants; Oximes; Phosgene; Skin
PubMed: 33297803
DOI: 10.1080/15376516.2020.1861670 -
Toxicology Letters Sep 2018Phosgene Oxime (CX, ClCNOH), a halogenated oxime, is a potent chemical weapon that causes immediate acute injury and systemic effects. CX, grouped together with... (Review)
Review
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. For this reason, it could be produced as a weaponized mixture with other chemical warfare agents to enhance their deleterious effects. The immediate devastating effects of CX and easy synthesis makes it a dangerous chemical with both military and terrorist potentials. Although CX is the most potent vesicating agent, it is one of the least studied chemical warfare agents and the pathophysiology as well as long term effects are largely unknown. CX exposure results in immediate pain and inflammation, and it mainly affects skin, eye and respiratory system. There are no antidotes available against CX-induced injury and the treatment is only supportive. This review summarizes existing knowledge regarding exposure, toxicity and the probable underlying mechanisms of CX compared to other important vesicants' exposure.
Topics: Animals; Antidotes; Arsenic Poisoning; Arsenicals; Blister; Chemical Warfare Agents; Humans; Irritants; Mustard Gas; Phosgene; Poisoning; Skin Diseases
PubMed: 29141200
DOI: 10.1016/j.toxlet.2017.11.011 -
Analytical Chemistry Dec 2017The meso-oxime-substituted-1,3,5,7-tetramethyl BODIPY (1-oxime) was developed into a colorimetric and fluorogenic probe to selectively detect and quantify phosgene. The...
The meso-oxime-substituted-1,3,5,7-tetramethyl BODIPY (1-oxime) was developed into a colorimetric and fluorogenic probe to selectively detect and quantify phosgene. The fast (<10 s) and sensitive (LOD = 0.09 ppb) phosgene detection is achieved by the conversion of the meso-oxime to the meso-nitrile, resulting in a large fluorescence turn-on response. The utility of 1-oxime was established for the visual detection of phosgene in solution and in a practical solid-state platform, making it a suitable candidate for on-site monitoring of phosgene gas exposure in the workplace.
PubMed: 29137453
DOI: 10.1021/acs.analchem.7b03316 -
Critical Care Clinics Oct 2005Vesicants (or blister agents) are cytotoxic alkylating compounds, which are chemical agents sometimes collectively known as mustard gas or simply as mustard. Other... (Review)
Review
Vesicants (or blister agents) are cytotoxic alkylating compounds, which are chemical agents sometimes collectively known as mustard gas or simply as mustard. Other blister agents are nitrogen mustard; sulfur mustard; lewisite, a vesicant that contains arsenic; and phosgene oxime, a halogenated oxime that possesses different properties and toxicity from the other agents. This article discusses history, toxicity, clinical presentation, and common treatment for vesicants.
Topics: Chemical Warfare; Decontamination; Diagnosis, Differential; Environmental Exposure; Eye Injuries; Humans; Irritants; Skin
PubMed: 16168310
DOI: 10.1016/j.ccc.2005.06.005 -
Toxicology and Applied Pharmacology Feb 2017Phosgene 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...
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. Thus, our goal was to examine the acute effects of CX following its cutaneous exposure in SKH-1 hairless mice to help establish a relevant injury model. Results from our study show that topical cutaneous exposure to CX vapor causes blanching of exposed skin with an erythematous ring, necrosis, edema, mild urticaria and erythema within minutes after exposure out to 8h post-exposure. These clinical skin manifestations were accompanied with increases in skin thickness, apoptotic cell death, mast cell degranulation, myeloperoxidase activity indicating neutrophil infiltration, p53 phosphorylation and accumulation, and an increase in COX-2 and TNFα levels. Topical CX-exposure also resulted in the dilatation of the peripheral vessels with a robust increase in RBCs in vessels of the liver, spleen, kidney, lungs and heart tissues. These events could cause a drop in blood pressure leading to shock, hypoxia and death. Together, this is the first report on effects of CX cutaneous exposure, which could help design further comprehensive studies evaluating the acute and chronic skin injuries from CX topical exposure and elucidate the related mechanism of action to aid in the identification of therapeutic targets and mitigation of injury.
Topics: Administration, Cutaneous; Animals; Edema; Erythema; Irritants; Male; Mice; Mice, Hairless; Oximes; Phosgene; Skin; Skin Diseases
PubMed: 28087322
DOI: 10.1016/j.taap.2017.01.003 -
Chemical Communications (Cambridge,... Apr 2022Herein, an aggregation-induced emission (AIE)-based sensor, 4-(1,2,2-triphenylvinyl)benzoxime (TPE-phos), has been rationally designed for phosgene detection. The sensor...
Herein, an aggregation-induced emission (AIE)-based sensor, 4-(1,2,2-triphenylvinyl)benzoxime (TPE-phos), has been rationally designed for phosgene detection. The sensor has a tetraphenylethylene unit combined with an oxime moiety. TPE-phos undergoes nitrile formation after the oxime group reacts with phosgene, which will give a significant "light-up" fluorescence due to the AIE effect within seconds.
Topics: Coloring Agents; Oximes; Phosgene; Spectrometry, Fluorescence
PubMed: 35403642
DOI: 10.1039/d2cc00745b -
Environmental Science. Processes &... Jul 2023Sensing of gaseous environment pollutants and health hazards is in demand these days and in this regard, lethal phosgene has emerged as a leading entrant. In this...
Sensing of gaseous environment pollutants and health hazards is in demand these days and in this regard, lethal phosgene has emerged as a leading entrant. In this contribution, we have successfully developed a facile chemodosimeter (ANO) based on an anthracene fluorophore and oxime recognition site with an interesting mechanism to sense lethal phosgene evolved from bleaching powder, a very popular disinfectant and sanitizer. The ANO probe is highly competent in recognizing deadly phosgene in solution and in the gaseous phase with a detection limit in the nanomolar range (1.52 nM). The sensing mechanism is confirmed by UV-vis, emission spectroscopy, mass spectrometry, and computational studies.
Topics: Phosgene; Cost-Benefit Analysis; Spectrometry, Fluorescence; Gases; Fluorescent Dyes
PubMed: 37345355
DOI: 10.1039/d3em00171g -
The Journal of Pharmacology and... Jan 2024Phosgene oxime (CX), categorized as a vesicating chemical threat agent, causes effects that resemble an urticant or nettle agent. CX is an emerging potential threat...
Phosgene oxime (CX), categorized as a vesicating chemical threat agent, causes effects that resemble an urticant or nettle agent. CX is an emerging potential threat agent that can be deployed alone or with other chemical threat agents to enhance their toxic effects. Studies on CX-induced skin toxicity, injury progression, and related biomarkers are largely unknown. To study the physiologic changes, skin clinical lesions and their progression, skin exposure of SKH-1 and C57BL/6 mice was carried out with vapor from 10 l CX for 0.5-minute or 1.0-minute durations using a designed exposure system for consistent CX vapor exposure. One-minute exposure caused sharp (SKH-1) or sustained (C57BL/6) decrease in respiratory and heart rate, leading to mortality in both mouse strains. Both exposures caused immediate blanching, erythema with erythematous ring (wheel) and edema, and an increase in skin bifold thickness. Necrosis was also observed in the 0.5-minute CX exposure group. Both mouse strains showed comparative skin clinical lesions upon CX exposure; however, skin bifold thickness and erythema remained elevated up to 14 days postexposure in SKH-1 mice but not in C57BL/6 mice. Our data suggest that CX causes immediate changes in the physiologic parameters and gross skin lesions resembling urticaria, which could involve mast cell activation and intense systemic toxicity. This novel study recorded and compared the progression of skin injury to establish clinical biomarkers of CX dermal exposure in both the sexes of two murine strains relevant for skin and systemic injury studies and therapeutic target identification. SIGNIFICANCE STATEMENT: Phosgene oxime (CX), categorized as a vesicating agent, is considered as a potent chemical weapon and is of high military and terrorist threat interest since it produces rapid onset of severe injury as an urticant. However, biomarkers of clinical relevance related to its toxicity and injury progression are not studied. Data from this study provide useful clinical markers of CX skin toxicity in mouse models using a reliable CX exposure system for future mechanistic and efficacy studies.
Topics: Animals; Mice; Phosgene; Disease Models, Animal; Mustard Gas; Mice, Inbred C57BL; Skin; Irritants; Erythema; Biomarkers; Oximes; Chemical Warfare Agents
PubMed: 37652710
DOI: 10.1124/jpet.123.001718 -
Chemico-biological Interactions Dec 2021Since their use during the First World War, Blister agents have posed a major threat to the individuals and have caused around two million casualties. Major incidents... (Review)
Review
Since their use during the First World War, Blister agents have posed a major threat to the individuals and have caused around two million casualties. Major incidents occurred not only due to their use as chemical warfare agents but also because of occupational hazards. Therefore, a clear understanding of these agents and their mode of action is essential to develop effective decontamination and therapeutic strategies. The blister agents have been categorised on the basis of their chemistry and the biological interactions that entail post contamination. These compounds have been known to majorly cause blisters/bullae along with alkylation of the contaminated DNA. However, due to the high toxicity and restricted use, very little research has been conducted and a lot remains to be clearly understood about these compounds. Various decontamination solutions and detection technologies have been developed, which have proven to be effective for their timely mitigation. But a major hurdle seems to be the lack of proper understanding of the toxicological mechanism of action of these compounds. Current review is about the detailed and updated information on physical, chemical and biological aspects of various blister agents. It also illustrates the mechanism of their action, toxicological effects, detection technologies and possible decontamination strategies.
Topics: Alkylating Agents; Arsenicals; Blister; Chemical Warfare Agents; Decontamination; Eye; Humans; Lung; Models, Biological; Mustard Compounds; Oximes; Phosgene; Skin
PubMed: 34634268
DOI: 10.1016/j.cbi.2021.109654 -
Forensic Science Review Jul 2014Chemical weapons have given the human experience of warfare a uniquely terrifying quality that has inspired a general repugnance and led to periodic attempts to ban... (Review)
Review
Chemical weapons have given the human experience of warfare a uniquely terrifying quality that has inspired a general repugnance and led to periodic attempts to ban their use. Nevertheless, since ancient times, toxic agents have been consistently employed to kill and terrorize target populations. The evolution of these weapons is examined here in ways that may allow military, law enforcement, and scientific professionals to gain a perspective on conditions that, in the past, have motivated their use - both criminally and as a matter of national policy during military campaigns. Special emphasis is placed on the genocidal use of chemical weapons by the regime of Saddam Hussein, both against Iranians and on Kurdish citizens of his own country, during the Iran-Iraq War of 1980-88. The historical development of chemical weapons use is summarized to show how progressively better insight into biochemistry and physiology was adapted to this form of warfare. Major attributes of the most frequently used chemical agents and a description of how they affected military campaigns are explained. Portions of this review describing chemical-casualty care devote particular focus to Iranian management of neurotoxic (nerve) agent casualties due to the unique nature of this experience. Both nerve and blistering "mustard" agents were used extensively against Iranian forces. However, Iran is the only nation in history to have sustained large-scale attacks with neurotoxic weapons. For this reason, an understanding of the successes and failures of countermeasures to nerve-agent use developed by the Iranian military are particularly valuable for future civil defense and military planning. A detailed consideration of these strategies is therefore considered. Finally, the outcomes of clinical research into severe chronic disease triggered by mustard-agent exposure are examined in the context of the potential of these outcomes to determine the etiology of illness among US and Allied veterans of the 1991 Persian Gulf War.
PubMed: 26227026
DOI: No ID Found