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Epidemiological studies of lung cancer in Japanese mustard gas workers.

Until the end of the Second World War, a poison gas manufacturing plant was operating on Okunojima, an island in the Seto Inland Sea. Of the gases produced there, mustard gas and Lewisite were found to be associated with various malignant tumors including lung cancer. The mortality rate for lung cancer in workers directly or indirectly involved in the production of poison gas was significantly higher than that of workers not involved in the production there. Lung cancer caused by poison gas was characterized by the following features: it was found as a central pulmonary carcinoma and was distributed from the upper airway to the hilar region. Squamous cell carcinoma and undifferentiated carcinoma predominated, whereas adenocarcinoma and other types were rare. Retired workers who had been engaged in the manufacture of mustard gas were found to have depressed immunological competence. We therefore started to enhance immunological competence with the use of Nocardia rubra cell wall skeleton (N-CWS) in order to prevent carcinogenesis. To date, no conclusion has been reached on its effectiveness in preventing carcinogenesis, however, we do expect it to be effective.

Humans↗

Skin manifestations of mustard gas in a group of 14 children and teenagers: a clinical study.

BACKGROUND: During the Iraq-Iran war (1980-1988), a group of patients exposed to mustard gas (one of the chemical warfare agents used by Iraq) were referred to our dermatology department. This group included a subgroup of 14 children and teenagers. In this article, we attempted to review the skin manifestations of these patients. METHODS: A group of patients, including 14 children and teenagers, exposed to mustard gas were studied. Laboratory tests including blood cell counts, hemoglobin, hematocrit, urine analysis, etc., were determined. RESULTS: Among the most frequent disorders were facial involvement (78%), which dominated the clinical picture, followed by genital (42%), truncal, and axillary lesions (both 14%). Eosinophilia was the most prominent laboratory disorder seen in 12% of the patients. Skin lesions started 4-18 hours after exposure. Erythema developed within 20-30 hours after exposure, followed by blisters. CONCLUSIONS: The time of onset of manifestations had been shorter and severity of the lesions higher in children and teenagers compared with adults. Both phenomena could be attributed to the more delicate skin of the young patients. Genital manifestations were less frequent in this subgroup while ophthalmic, pulmonary, and gastrointestinal lesions were more frequently encountered in children than in adults. The unfortunate consequences of exposure to such chemicals reminds once again the urgency of international treaties to effectively ban the use of chemical weapons.

Adolescent↗

A mediational model of PTSD in World War II veterans exposed to mustard gas.

Structural equation modeling (SEM) was used to examine associations among trauma-related contextual factors, initial psychological reactions, social support, and subsequent disclosure on posttraumatic stress disorder (PTSD) symptoms in a sample of World War II (WWII) veterans exposed to mustard gas (N = 305). A structural model suggested that initial psychological reaction mediated the relationship between variables related to the context of mustard gas exposure and severity of PTSD symptoms 50 years later. Unexpectedly, social support appeared to be positively related to PTSD symptoms, and not related to the contextual variables or initial psychological reactions. These findings contribute to our understanding of PTSD in older veterans, and have relevance for early intervention services to prevent PTSD among those at risk for exposure to toxic agents.

Aged↗

Skin toxicokinetics of mustard gas in the guinea pig: effect of hypochlorite and safety aspects.

Sulfur mustard (SM, mustard gas) is a chemical warfare vesicant that rapidly penetrates the skin due to its hydrophobicity. This study measured the rate of SM disappearance from the skin after topical application of the vesicant. In both fur-covered and hairless animals, the remaining toxicant levels measured 60 min after exposure to undiluted SM were 0.6% and 0.3%, respectively, of the initially applied SM amount. However, SM concentration reached 0.4% of the initial dose 3 h following exposure in female fur-covered guinea pigs. SM quantities extracted from skin of male fur-covered and hairless guinea pigs immediately after 16 min of exposure to SM vapor were 12.2 and 21.8 microg, respectively; levels declined to 1.6 and 1.7 microg at 30 and 15 min following termination of exposure of male fur-covered and hairless guinea pigs, respectively. Three swabbing treatments of undiluted SM-exposed skin with gauze pads soaked in 0.5% hypochlorite caused 68% reduction in skin SM content. Similar findings were obtained when hypochlorite was replaced by water (64% reduction). SM content in the gauze pads was 59, 38 and 25 microg, respectively, for the first, second and third decontamination processes with water. No SM was detected in the gauze pads soaked with hypochlorite. In vitro studies showed that incubation of SM with 0.5% hypochlorite at a ratio of 10:1 (v/v) did not cause SM inactivation, whereas 4% hypochlorite reduced SM levels by 17%. However, at a decontaminant:SM ratio of 1000:1, 0.5% and 4% hypochlorite reduced SM levels by 92% and 99%, respectively. These findings are important for health authorities and regulatory agencies in planning precautionary steps to be taken in case of emergency and in routine laboratory work.

Animals↗

Clinical and morphological findings on mustard gas [bis(2-chloroethyl)sulfide] poisoning.

In 1984 and 1985, a total of eleven Iranian patients were transferred to hospitals in Munich, Germany, after a reported gas attack in the Iran-Iraq war. The initial symptoms and pretreatment in Teheran, Iran, as well as the admittance examination data, the clinical courses of the patients, and the clinical laboratory data in Germany, are reported. The main injuries were to the skin, the eyes, and the respiratory tract. One patient stopped breathing suddenly on the third day of treatment (eight days after the exposure). A large piece of mucous membrane blocking a bronchus was removed during an immediate bronchoscopy, but attempts at resuscitation failed. The most important autopsy findings in this case were severe pseudomembranous inflammation of the trachea and the bronchial tubes. The histological findings are reported. Chemical proof of the poison (mustard gas) was established. A review of the history of chemical warfare, the physical and chemical properties of mustard gas, and a literature survey of clinical findings (including, especially, experiences from World Wars I and II) contribute to the understanding of the actual cases.

Adult↗

[Carcinogenesis due to mustard gas exposure in man, important sign for therapy with alkylating agents].

Sulphur-mustard and nitrogen-mustard are known to act as carcinogens in animal experiments. A similar effect in humans was demonstrated in 245 workers previously exposed occupationally to mustard gas and followed for over 20 years. There was a statistically significant increase in malignant tumours, especially bronchial carcinoma, bladder carcinoma and leukaemia. These findings underline the need for using alkylating agents of the mustard type exclusively in the treatment of malignant neoplasms. Immunosuppression with alkylating agents in the treatment of chronic inflammatory diseases associated with a long life expectancy is no longer justified.

Adult↗

Determination of thiodiglycol, a mustard gas hydrolysis product by gas chromatography-mass spectrometry after tert-butyldimethylsilylation.

A method for determining thiodiglycol (TDG), a mustard gas hydrolysis product in water, serum and urine samples using gas chromatography-mass spectrometry (GC-MS) after tert-butyldimethylsilylation (TBDMS) is described. Quantitation of TDG was performed by measuring the respective peak area on the extracted ion chromatogram of m/z 293, using an internal standard, the TDG homologue, thiodipropanol, peak area of which was measured as m/z 321. The presence of salts in the sample solution not only suppressed the loss of TDG by vaporization during the evaporation of water, but also facilitated the rate of production of di-silylated derivative, bis(tert-butyldimethylsilyoxylethyl)sulfide (TDG-(TBDMS)2). Under the pretreatment conditions used, in which 0.5 ml of water sample supplemented with 100 microM potassium chloride was evaporated to dryness under reduced pressure, followed by reaction with N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide at 60 degrees C for 1 h, TDG-(TBDMS)2 was reproducibly detected with about a 55% recovery and a limit of detection (LOD, scan mode, S/N = 3) of 5.4 ng/ml. TDG was also determined by GC-MS from a 0.5 ml serum sample (after perchloric acid deproteinization) and from a 0.1 ml urine sample, after TBDMS derivatization. The LOD was determined to be 7.0 and 110 ng/ml for serum and urine, respectively.

Gas Chromatography-Mass Spectrometry↗

Cancer of the larynx and other occupational hazards of mustard gas workers.

An attempt was made to tract 511 men and women who manufactured mustard gas during the 1939--1945 war. Despite limitations in the identifying data available, 428 (84%) were traced to the end of 1974. The numbers of deaths from all neoplasms combined (45) and from all other causes (136) were slightly greater than those expected from national death rates, but not significantly so. Two deaths were attributed to carcinoma of the larynx and one to carcinoma of the trachea, compared with an expected number of 0.40 (P less than 0.02). Carcinoma of the larynx was also mentioned on the death certificate of another man. Seven subjects are known to have developed cancer of the larynx, compared with 0.75 expected (P less than 0.001). Excess mortality was also observed from cancer of the lung, pneumonia and accidents, but the excesses were small and difficult to interpret.

Adult↗

[The bioutilization of thiodiglycol (a breakdown product of mustard gas): isolation of degraders and investigation of degradation conditions].

The Alcaligenes xylosoxydans subsp. denitrificans strain TD1 capable of degrading thiodiglycol (TDG), a breakdown product of mustard gas, was isolated from soil contaminated with breakdown products of this chemical warfare agent. The selected stable variant of TD1 (strain TD2) can grow on TDG with a lag phase of 4-8 h and a specific growth rate of 0.04-0.045 h-1. Optimal conditions for the biodegradation of TDG (pH, the concentration of TDG in the medium, and its relative content with respect to the bacterial biomass) were determined. TDG was found to be degraded with the formation of diglycolsulfoxide and thiodiglycolic acid. The data obtained can be used to develop approaches to the bioremediation of mustard gas-contaminated soils.

Alcaligenes↗

[Lung parenchymatous changes following mustard gas poisoning].

The authors present a late sequel of poisoning with dichlorodiethyl sulphide, also known as mustard gas or Ypérite, in a patient of 22 years of age--a late sequel not described in the literature to date. After the poisoning, a severe pulmonary fibrosis with pulmonary artery hypertension developed. A mediastinal emphysema that had so far been observed only during the acute intoxication phase, was evident even two years after the intoxication. Perivascular collections of air in the left lung communicating via the left hilus with the mediastinal air point to the existence of bronchus or lung parenchyma fistulas.

Adult↗