RESUMEN
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.tx.ovid.com) and PubMed (http://www.pubmed.org) search engines to perform MEDLINE searches for the terms 'sea-dumped chemical weapons', 'chemical warfare agents', and 'chemical munitions'. The searches returned 5863 articles. Irrelevant and non-English articles were excluded. A review of the references for these articles yielded additional relevant sources, with a total of 64 peer-reviewed articles cited in this paper. History and geography of chemical weapons dumping at sea: Hundreds of thousands of tons of chemical munitions were disposed off at sea following World War II. European, Russian, Japanese, and United States coasts are the areas most affected worldwide. Several areas in the Baltic and North Seas suffered concentrated large levels of dumping, and these appear to be the world's most studied chemical warfare agent marine dumping areas. Chemical warfare agents: Sulfur mustard, Lewisite, and the nerve agents appear to be the chemical warfare agents most frequently disposed off at sea. Multiple other type of agents including organoarsenicals, blood agents, choking agents, and lacrimators were dumped at sea, although in lesser volumes. Environmental concerns: Numerous geohydrologic variables contribute to the rate of release of chemical agents from their original casings, leading to difficult and inexact modeling of risk of release into seawater. Sulfur mustard and the organoarsenicals are the most environmentally persistent dumped chemical agents. Sulfur mustard in particular has a propensity to form a solid or semi-solid lump with a polymer coating of breakdown products, and can persist in this state on the ocean floor for decades. Rates of solubility and hydrolysis and levels of innate toxicity of a chemical agent are used to predict the risk to the marine environments. The organoarsenicals eventually breakdown into arsenic, and thus present an indefinite timeline for contamination. Generally, studies assaying sediment and water levels of parent chemical agents and breakdown products at dumpsites have found minimal amounts of relevant chemicals, although arsenic levels are typically higher in dumpsites than reference areas. Studies of marine organisms have not shown concerning amounts of chemical agents or breakdown products in tissue, but have shown evidence of chronic toxicity. There is believed to be minimal risk posed by seafood consumption. Microbiota assays of dumpsites are significantly altered in species composition compared to reference sites, which may imply unseen but significant changes to ecosystems of dumpsites. Human health concerns: The major human health risk at this time appears to arise from acute exposure to an agent by either accidental recovery of a chemical weapon on a fishing vessel, or by munitions washed ashore onto beaches. CONCLUSIONS: Improving technology continues to make the deep sea more accessible, thus increasing the risk of disturbing munitions lying on or buried in the seabed. Pipe laying, cable burying, drilling, scuba diving, trawling, and undersea scientific research are the activities posing the most risk. The long-term threat to the benthic habitat via increased arsenic concentrations, shifts in microbiota speciation, and chronic toxicity to vertebrates and invertebrates is not currently understood. The risk to the environment of massive release via disturbance remains a distinct possibility. Terrorist recovery and re-weaponization of chemical agents is a remote possibility.
Asunto(s)
Sustancias para la Guerra Química/análisis , Océanos y Mares , Animales , Organismos Acuáticos/efectos de los fármacos , Organismos Acuáticos/crecimiento & desarrollo , Arsenicales/análisis , Sustancias para la Guerra Química/toxicidad , Cianuros/análisis , Cianuros/toxicidad , Bases de Datos Factuales , Monitoreo del Ambiente , Europa (Continente) , Peces/crecimiento & desarrollo , Sedimentos Geológicos/análisis , Humanos , Japón , Gas Mostaza/análisis , Gas Mostaza/toxicidad , Agentes Nerviosos/análisis , Agentes Nerviosos/toxicidad , Fosgeno/análisis , Fosgeno/toxicidad , Medición de Riesgo , Estados Unidos , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidad , omegacloroacetofenona/análisis , omegacloroacetofenona/toxicidadRESUMEN
The TRPA1 channel is activated by a number of pungent chemicals, such as allylisothiocyanate, present in mustard oil and thiosulfinates present in garlic. Most of the known activating compounds contain reactive, electrophilic chemical groups, reacting with cysteine residues in the active site of the TRPA1 channel. This covalent modification results in activation of the channel and has been shown to be reversible for several ligands. Commonly used tear gasses CN, CR and CS are also pungent chemicals, and in this study we show that they are extremely potent and selective activators of the human TRPA1 receptor. To our knowledge, these are the most potent TRPA1 agonists known to date. The identification of the molecular target for these tear gasses may open up possibilities to alleviate the effects of tear gasses via treatment with TRPA1 antagonists. In addition these results may contribute to the basic knowledge of the TRPA1 channel that is gaining importance as a pharmacological target.
Asunto(s)
Canales de Calcio/efectos de los fármacos , Dibenzoxazepinas/toxicidad , Proteínas del Tejido Nervioso/efectos de los fármacos , Gases Lacrimógenos/toxicidad , Canales de Potencial de Receptor Transitorio/efectos de los fármacos , o-Clorobencilidenomalonitrila/toxicidad , omegacloroacetofenona/toxicidad , Canales de Calcio/metabolismo , Células Cultivadas , Sistemas de Liberación de Medicamentos , Electrofisiología , Humanos , Proteínas del Tejido Nervioso/agonistas , Proteínas del Tejido Nervioso/metabolismo , Canal Catiónico TRPA1 , Canales de Potencial de Receptor Transitorio/agonistas , Canales de Potencial de Receptor Transitorio/metabolismoRESUMEN
Irritant incapacitants, also called riot control agents, lacrimators and tear gases, are aerosol-dispersed chemicals that produce eye, nose, mouth, skin and respiratory tract irritation. Tear gas is the common name for substances that, in low concentrations, cause pain in the eyes, flow of tears and difficulty in keeping the eyes open. Only three agents are likely to be deployed: (i) 1-chloroacetophenone (CN); (ii) 2-chlorobenzylidene malononitrile (CS); or (iii) dibenz[b,f]-1,4-oxazepine (CR). CN is the most toxic lacrimator and at high concentrations has caused corneal epithelial damage and chemosis. It has accounted for at least five deaths, which have resulted from pulmonary injury and/or asphyxia. CS is a 10-times more potent lacrimator than CN but is less systemically toxic. CR is the most potent lacrimator with the least systemic toxicity and is highly stable. CN, CS and CR cause almost instant pain in the eyes, excessive flow of tears and closure of the eyelids, and incapacitation of exposed individuals. Apart from the effects on the eyes, these agents also cause irritation in the nose and mouth, throat and airways and sometimes to the skin, particularly in moist and warm areas. In situations of massive exposure, tear gas, which is swallowed, may cause vomiting. Serious systemic toxicity is rare and occurs most frequently with CN; it is most likely to occur when these agents are used in very high concentrations within confined non-ventilated spaces. Based on the available toxicological and medical evidence, CS and CR have a large safety margin for life-threatening or irreversible toxic effects. There is no evidence that a healthy individual will experience long-term health effects from open-air exposures to CS or CR, although contamination with CR is less easy to remove.
Asunto(s)
Dibenzoxazepinas/toxicidad , Irritantes/toxicidad , Sustancias para Control de Disturbios Civiles/toxicidad , Gases Lacrimógenos/toxicidad , o-Clorobencilidenomalonitrila/toxicidad , omegacloroacetofenona/toxicidad , HumanosRESUMEN
In 1996, the New York State Department of Health was charged by the State Legislature to develop regulations regarding the types of self-defense spray devices which could lawfully be purchased, possessed, and used in New York State. Prior to this legislation, sale or possession of self-defense spray devices in New York State was illegal. The Department of Health used existing data to evaluate three commonly used self-defense spray active ingredients (oleoresin capsicum, o-chlorobenzylidene malononitrile, and 2-chloroacetophenone) with respect to their relative toxicity and their involvement in accidental poisonings. Based on the balance of the available information, the Department of Health determined that oleoresin capsicum posed a lower public health concern than o-chlorobenzylidene malononitrile or 2-chloroacetophenone, and developed a rule that specifies oleoresin capsicum as the only active ingredient to be used in self-defense sprays for sale and use in New York State.
Asunto(s)
Aerosoles/toxicidad , Exposición a Riesgos Ambientales/efectos adversos , Extractos Vegetales/toxicidad , Compuestos Policíclicos/toxicidad , Administración en Salud Pública/legislación & jurisprudencia , Administración en Salud Pública/normas , omegacloroacetofenona/toxicidad , Accidentes , Administración Oral , Animales , Compuestos de Bencilideno , Femenino , Cobayas , Humanos , Exposición por Inhalación , Dosificación Letal Mediana , Masculino , Ratones , New York , Evaluación de Programas y Proyectos de Salud , Conejos , Ratas , Medición de Riesgo/estadística & datos numéricos , Pruebas de Toxicidad AgudaRESUMEN
The kinetics of chloracetophenone (CN) in rabbit eyes was studied by high-performance liquid chromatography on a model of experimental third-degree burn. By the end of the first hour after exposure to the lacrimate, CN content was high in all the studied tissues: 28.5 +/- 0.563 x 10(-1) mg/kg in the cornea, 5.08 +/- 0.193 x 10(-1) mg/kg in the anterior chamber humor, and 3.26 +/- 0.123 x 10(-1) mg/kg in the vitreous. After 6 h the content of the irritant dropped almost threefold and was 8.5 +/- 0.403 x 10(-1) mg/kg in the cornea, 1.23 +/- 0.062 x 10(-1) mg/kg in the anterior chamber humor, and 0.017 +/- 0.006 x 10(-1) mg/kg in the vitreous. By the end of 24 h these values were 6.6 +/- 0.221, 1.46 +/- 0.123, and 0.015 +/- 0.005 x 10(-1) mg/kg, respectively, and by day 14 only trace amounts of CN were detected. Hence, CN in the Cheremukha gas balloons can penetrate into the inner structures of the eye and cause severe injuries. Persistence of CN for up to 14 days disordered the metabolic processes and anatomy of the eye. High content of CN during the first 7 days after burn requires adequate pathogenetic therapy.
Asunto(s)
Quemaduras Químicas , Quemaduras Oculares/inducido químicamente , Ojo/química , Irritantes/análisis , Gases Lacrimógenos/análisis , omegacloroacetofenona/análisis , Animales , Cámara Anterior/química , Cromatografía Líquida de Alta Presión , Córnea/química , Ojo/efectos de los fármacos , Irritantes/toxicidad , Conejos , Gases Lacrimógenos/toxicidad , Factores de Tiempo , Cuerpo Vítreo/química , omegacloroacetofenona/toxicidadRESUMEN
The glutathione (GSH) depleting effect of 2-chloroacetophenone (CN) was studied in freshly isolated rat hepatocytes. CN proved to be more effective in depleting GSH than diethylmaleate, phorone or styrene oxide. The reaction between GSH and CN followed a 1:1 stoichiometry, allowing adjustment of cellular GSH concentrations at distinct levels. After incubating cells (8 mg protein/ml) with 200 mumol CN/l for 5 min, GSH depletion was almost complete without signs of cytotoxicity. At 300 mumol/l CN, GSH depletion persisted, and cytotoxicity occurred after 30 min. Activities of cytochrome P450 dependent enzymes, even at concentrations up to 500 mumol CN/l, were only marginally affected. Therefore, CN is of particular value for in vitro studies at decreased availability of GSH.
Asunto(s)
Glutatión/metabolismo , Hígado/efectos de los fármacos , omegacloroacetofenona/toxicidad , Animales , Células Cultivadas , Cetonas/toxicidad , Hígado/metabolismo , Masculino , Maleatos/toxicidad , Ratas , Ratas WistarRESUMEN
Inhalation toxicity following exposure to 1-Chloroacetophenone (CN) and Dibenz(b,f)-1,4 oxazepine (CR) aerosols for 60 min at sublethal concentrations were studied in rats. The dynamic surface tension (gamma max and stability ratio) of lung homogenate increased significantly on CN exposure. The lung mechanics studies revealed a significant increase in compliance in CN exposed rats. CR, on the other hand did not influence any of the above variables except for a decrease in compliance. Total lung phospholipids and sphingomyelin contents decreased significantly following exposure to CN, while CR exposure produced an increase in sphingomyelin, reduction in phosphatidylcholine and ethanolamine, with no change in total phospholipid contents. Histomorphological observations indicated cellular degeneration in the epithelium of the bronchiole and alveolar septal-wall thickening due to the presence of an increased number of mononuclear cells in CN exposed rats. However, CR induced inflammatory reaction and enlargement of respiratory air spaces. It is concluded that of the two sensory irritants (tear gases) examined, CN is potentially more toxic compared to CR in rats.
Asunto(s)
Dibenzoxazepinas/toxicidad , Pulmón/efectos de los fármacos , Surfactantes Pulmonares/efectos de los fármacos , Mecánica Respiratoria/efectos de los fármacos , Gases Lacrimógenos/toxicidad , omegacloroacetofenona/toxicidad , Administración por Inhalación , Aerosoles , Animales , Dibenzoxazepinas/administración & dosificación , Pulmón/química , Pulmón/patología , Pulmón/fisiología , Masculino , Fosfolípidos/análisis , Alveolos Pulmonares/efectos de los fármacos , Alveolos Pulmonares/patología , Ratas , Pruebas de Función Respiratoria , Tensión Superficial/efectos de los fármacos , omegacloroacetofenona/administración & dosificaciónRESUMEN
Toxicological evaluation was made on the effects of two peripheral sensory irritants (tear gases): 1-chloroacetophenone (CN) and dibenz[b,f]-1,4-oxazepine (CR). Animals had a 15-min daily inhalation exposure to average vapour concentrations of 87.6 mg CN m-3 or 1008 mg CR m-3 (both equal to 0.05 LC50) for 5 or 10 days and were sacrificed 24 h after the last exposure, when biochemical and histopathological observations were made. Both chemicals caused a significant decrease in body weight gain. Histological changes in lung, liver and kidneys were more severe after 10 than after 5 days of exposure and were more severe in CN-exposed than in CR-exposed mice. Organ weight to body weight ratios remained normal except for the spleen to body weight ratio, which decreased in CN-exposed mice after both 5 and 10 days of exposure. Biochemical indicators showed a toxic response only in CN-exposed mice, but the only consistent change was an increase in blood glucose. Hepatic alkaline phosphatase was not influenced, malondialdehyde concentration and acid phosphatase activity were increased only after 5 days of exposure and liver GSH concentration decreased after 10 days of exposure. Results indicate that CN is not only more toxic than CR in absolute terms but is also more toxic at the 5% level of their LC50.
Asunto(s)
Dibenzoxazepinas/toxicidad , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Pulmón/efectos de los fármacos , omegacloroacetofenona/toxicidad , Administración por Inhalación , Alanina Transaminasa/efectos de los fármacos , Animales , Aspartato Aminotransferasas/efectos de los fármacos , Glucemia/efectos de los fármacos , Nitrógeno de la Urea Sanguínea , Peso Corporal/efectos de los fármacos , Colinesterasas/efectos de los fármacos , Riñón/patología , Hígado/patología , Pulmón/patología , Masculino , RatonesRESUMEN
Lung damage caused by inhalation (single exposure for 60 min) of sublethal concentration of pure aerosols of dibenz(b,f)-1,4-oxazepine (CR) and 1-chloroacetophenone (CN) have been examined at different time intervals in rats. The damage was not severe with CR (2830 mg.m-3) but in the case of CN (60.26 mg.m-3) it was evident up to 30th day post exposure. Necrobiosis, attenuation of bronchiolar epithelium, edema in the air ways and also in the lumen of alveoli leading to substantial changes in the histoarchitecture of the lung were observed during CN exposure. On the other hand CR caused degenerative changes which disappeared on 30th day.
Asunto(s)
Carcinógenos/toxicidad , Dibenzoxazepinas/toxicidad , Irritantes/toxicidad , Enfermedades Pulmonares/patología , omegacloroacetofenona/toxicidad , Administración por Inhalación , Aerosoles , Animales , Carcinógenos/administración & dosificación , Dibenzoxazepinas/administración & dosificación , Irritantes/administración & dosificación , Enfermedades Pulmonares/inducido químicamente , Ratas , Factores de Tiempo , omegacloroacetofenona/administración & dosificaciónRESUMEN
Tear gas has gained widespread acceptance as a means of controlling civilian crowds and subduing barricaded criminals. The most widely used forms of tear gas have been o-chlorobenzylidenemalononitrile and omega-chloroacetophenone. Proponents of their use claim that, if used correctly, the noxious effects of exposure are transient and of no long-term consequences. The use of tear gas in recent situations of civil unrest, however, demonstrates that exposure to the weapon is difficult to control and indiscriminate, and the weapon is often not used correctly. Severe traumatic injury from exploding tear gas bombs as well as lethal toxic injury have been documented. Moreover, available toxicological data are deficient as to the potential of tear gas agents to cause long-term pulmonary, carcinogenic, and reproductive effects. Published and recent unpublished in vitro tests have shown o-chlorobenzylidenemalononitrile to be both clastogenic and mutagenic. Sadly, the nature of its use renders analytic epidemiologic investigation of exposed persons difficult. In 1969, eighty countries voted to include tear gas agents among chemical weapons banned under the Geneva Protocol. There is an ongoing need for investigation into the full toxicological potential of tear gas chemicals and renewed debate on whether their use can be condoned under any circumstances.
Asunto(s)
Gases Lacrimógenos/efectos adversos , Adulto , Desórdenes Civiles , Exposición a Riesgos Ambientales , Humanos , Corea (Geográfico) , o-Clorobencilidenomalonitrila/efectos adversos , o-Clorobencilidenomalonitrila/toxicidad , omegacloroacetofenona/efectos adversos , omegacloroacetofenona/toxicidadRESUMEN
Chloroacetophenone (CN) is used as a tear gas for riot control and as a kind of chemical Mace against small groups or individuals. Among other side-effects, CN can evoke toxic and allergic contact dermatitis, and more rarely exanthematous or anaphylactic reactions. It is difficult to distinguish between toxic and allergic reactions both in the clinical picture of dermatitis as well as on the basis of skin test reactions. We report on a patient with allergic contact dermatitis, which first appeared 5 days after exposure to CN as a sign of primary sensitization, leading to an intense eczematous reaction in skin tests. Allergy to CN does not appear to represent a handicap in normal daily life because it is solely used as tear gas and is of little significance as regards "cross-allergies" to substances in the environment.
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Dermatitis por Contacto/etiología , Dermatosis Facial/inducido químicamente , Insecticidas/toxicidad , Compuestos Organofosforados , omegacloroacetofenona/toxicidad , Eccema/inducido químicamente , Humanos , Masculino , Pruebas del ParcheAsunto(s)
Contaminantes Químicos del Agua/toxicidad , Contaminantes del Agua/toxicidad , omegacloroacetofenona/análogos & derivados , Animales , Relación Dosis-Respuesta a Droga , Femenino , Cobayas , Dosificación Letal Mediana , Masculino , Concentración Máxima Admisible , Ratones , Ratas , Factores de Tiempo , omegacloroacetofenona/toxicidadAsunto(s)
Contaminantes Ocupacionales del Aire , Contaminantes Atmosféricos , omegacloroacetofenona/análogos & derivados , Animales , Relación Dosis-Respuesta a Droga , Exposición a Riesgos Ambientales , Cobayas , Dosificación Letal Mediana , Concentración Máxima Admisible , Ratones , Conejos , Ratas , Factores de Tiempo , omegacloroacetofenona/envenenamiento , omegacloroacetofenona/toxicidadRESUMEN
The comparative acute toxicity of two peripheral sensory irritant materials, 1-chloroacetophenone (CN) and 2-chlorobenzylidene malononitrile (CS), has been investigated in several species of small mammal using solutions in polyethylene glycol 300 for intravenous, intraperitoneal and oral administration, and as pure aerosols for inhalation exposure. Additionally, the comparative potency for inducing primary contact dermatitis was studied. CN and CS were found to be about equitoxic by intravenous and intraperitoneal injection, but CS was significantly less toxic by the oral and inhalation routes and less likely to cause non-lethal tissue damage than CN.
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Nitrilos/toxicidad , o-Clorobencilidenomalonitrila/toxicidad , omegacloroacetofenona/toxicidad , Administración Oral , Aerosoles , Animales , Femenino , Cobayas , Infusiones Parenterales , Inyecciones Intravenosas , Irritantes , Dosificación Letal Mediana , Masculino , Ratones , Conejos , Ratas , Piel/efectos de los fármacos , o-Clorobencilidenomalonitrila/administración & dosificación , omegacloroacetofenona/administración & dosificaciónRESUMEN
Dibenz(b,f)-1,4-oxazepine (CR), a potent peripheral sensory irritant material, has been shown to have a very low acute lethal and sub-lethal toxicity by intravenous, intraperitoneal, oral, percutaneous and inhalation routes to several species of laboratory mammal. There was no organ-specific pathology. Comparison of the acute toxicity of CR with that of two other peripheral sensory irritants, 1-chloroacetophenone (CN) and 2-chlorobenzyl-lidene malononitrile (CS), shows CR to be significantly less toxic than either of them. Pyrotechnically generated CR smoke was more toxic than pure (thermally generated) aerosols of CR; this was due to the presence of pyrotechnic decomposition products in the atmosphere from the burning of the smoke generating composition. However, the median lethal toxicity of pyrotechnically generated CR smoke was very significantly less than that of either pyrotechnically generated CN or CS smokes. Short-term cumulative toxicity did not occur following multiple oral dosing with CR. The acute toxicology of three ether intermediates encountered in the synthesis of CR from 1-chloro-2-nitrobenzene and sodium phenoxide (2-nitrodiphenyl ether, 2-aminodiphenyl ether and 2-formamidodiphenyl ether) was investigated; all three ethers were found to be less acutely toxic than CR itself.