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PubMed1987

Mustard gas: clinical, toxicological, and mutagenic aspects based on modern experience.

Based on a study of the literature and our own experience treating fisherman poisoned by mustard gas, this article outlines the clinical effects, and toxicological and mutagenic properties of the agent. Mustards are very persistent chemical agents that easily penetrate clothing. Mustard gas usually causes clinical symptoms after the liquid penetrates the skin or the vapor is inhaled. Skin lesions are similar to first- or second-degree burns and usually heal spontaneously in 4 to 6 weeks. Eye symptoms are photophobia and reduced vision. Following inhalation of the agent, pulmonary edema and long-term dyspnea may be seen. As mustard gas is an alkylating substance, it is conceivable that the risk of developing cancer may be increased, as observed in people who were involved with the production of mustard gas and in animals exposed to the gas. Also, transient significantly increased sister chromatid exchange rates have been found in fishermen exposed to mustard gas. Patients exposed to mustard gas must be treated immediately after exposure. Treatment should consist of cleaning of the exposed skin and clothes with an antigas powder and water and soap. The skin lesions should be treated as burns. Eye lesions and respiratory problems should be treated symptomatically.

Eye Diseases↗
PubMed1987

Concentrations of mustard gas [bis(2-chloroethyl)sulfide] in the tissues of a victim of a vesicant exposure.

An Iranian soldier died at a toxicological intensive care unit at Munich seven days after a vesicant exposure. At the autopsy the typical symptoms of mustard gas intoxication were found. The vesicant was detected qualitatively by gas chromatography-mass spectrometry (GC-MS) in the abdominal fat and quantified in the tissues and in the body fluids by the following method: (1) extraction by dichloromethane, (2) cleanup of the extracts by thin-layer chromatography (TLC) on silica plates, (3) extractive derivatization with gold-chloride, and (4) quantitative determination by electrothermal atomic absorption spectrometry (ET-AAS). The equal extracts, after heating, served for blanks. The following concentrations were found (milligrams of mustard gas/kilograms of tissue wet weight): brain 10.7, cerebrospinal fluid 1.9, liver 2.4, kidney 5.6; spleen 1.5, lung 0.8, muscle 3.9, fat 15.1, skin 8.4, skin with subcutaneous fatty tissue 11.8, liquid from a skin blister: below detection limit, blood 1.1, and urine: below detection limit.

Adult↗
PubMed1987

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↗
PubMedDate not supplied

[Treatment of psoriasis with dichlorodiethyl sulfide].

A report is given of the use of dichlorodiethyl-sulfide (ypérite) in ointment form in a concentration of 1: 20,000 in the treatment of psoriasis. The effect of the treatment was followed in 59 patients. Healing or marked improvement occurred in 44. In in-patients the average duration of treatment was 16 days and in out-patients 48 days. When compared with other methods of treatment the method of application is very simple and its effect rapid. So that with a shorter average duration of treatment a higher percentage of patients is healed.

Adolescent↗
PubMed1986

Intramuscular prednisolone pretreatment does not influence the dermal lesions induced by topical sulfur mustard.

The effect of a single intramuscular injection of prednisolone sodium phosphate (14.3 mg/kg) on the development and severity of dermal lesions induced by topical sulfur mustard was investigated in guinea pigs. Control animals received sulfur mustard alone, topical sulfur mustard and intramuscular saline, intramuscular prednisolone alone, or intramuscular saline alone. With topical sulfur mustard alone there were typical mustard lesions consisting of epidermal necrosis and hyalinization, with acute inflammation and necrosis in the dermis, the severity and extent of which were dose-related. Systemic prednisolone therapy had no influence on the nature, severity or progression of the dermal histopathologic response to topical sulfur mustard.

Animals↗
PubMed1986

[Cancer of the respiratory tract observed in workers having retired from a poison gas factory].

Okunojima, a small island in the Inland Sea of Japan, off the shore of Takehara city was notorious for the production of poison gases from 1927 to 1945. Of the gases produced there, yperite and lewisite were the most poisonous and caused severe residual damage. It has been ascertained by studies conducted to date that the retired workers of this poison gas factory have a high risk of various types of malignant tumors including cancers of the respiratory tract. Such cancers observed in the retired workers from the poison gas factory are characterized by the following clinical features. Cancers are mainly central-type tumors with the site of development distributed from the airway to the hilar region and histologically, squamous and undifferentiated cell carcinoma predominate. Recently, the occurrence of malignant tumors has been discussed in relation to suppressed immune competence. Such disturbance of the immunological surveillance system seems to induce malignant changes of normal cells. On the other hand, we have demonstrated that the retired workers often showed impaired immunity. Therefore we considered that potentiation of immunity might possibly prevent the occurrence of malignant tumors and we took steps to enhance the immune competence of the retired workers with N-CWS. Its effect in preventing carcinogenesis will be shown in the near future.

Aged↗
PubMed1979

[Treatment of psoriasis vulgaris with external sulfur mustard gas with particular reference to its potential carcinogenic risk. III. Clinical and experimental studies on the extent of percutaneous and inhalational uptake of sulfur mustard gas].

Concerning the often discussed carcinogenic risk of psoriasis treatment with 0.005% S-mustard-vaseline (so-called Russian Ointment) -- especially by inhalation -- 19 patients were treated with a radioactive labeled S-mustard-ointment and examined. The patients' whole bodies were inuncted for 1--2 days with about 50 g of radioactive S-mustard vaseline (U14C, 3 muCi/g). Afterwards the radioactivity was determined in the patients' expired air, blood, urine, and in their surrounding air. In three patients punch biopsy material from normal and psoriatic skin was assayed for radioactivity after combustion. In the skin, radioactivity distinctly decreased from the epidermis (13.1 pCi/mg) to the subcutis (0.77 pCi/mg) without significant differences between normal skin and psoriatic lesions as confirmed by autoradiography. In all samples of air, body fluids and tissue, definitive amounts of radioactivity were found, which, however, were far below the US-American MAK-values. Between skin surface and shirt, the values varied from 1.5 to 13.7 nCi/20 l air, at a distance of 2 meters by 0.3 nCi/100 l air, in the breath by 0.5 nCi/20 l. The radioactivity decreased to 1/10 of the maximum values after 1--2 hours. In blood the activity was at the limit of detection and was parallelled by the activity of the urine. Generally, 1--7% of the radioactivity applied to the skin was eliminated with the urine within one week. Thus, the carcinogenic risk may be very low in the external S-mustard therapy of psoriasis and other skin diseases.

Air↗
PubMed1985

Inflammatory mediators and modulators released in organ culture from rabbit skin lesions produced in vivo by sulfur mustard. I. Quantitative histopathology; PMN, basophil, and mononuclear cell survival; and unbound (serum) protein content.

When applied topically to the skin of rabbits in vivo, sulfur mustard (SM), the vesicant used in World War I, produced a slowly developing inflammatory response, which peaked in size at 1 and 2 days, ulcerated within 3 days, and reepithelialized by 10 days. Histologically, basophils and polymorphonuclear leukocytes (PMNs) were common in both early and late lesions, and the crust over the ulcers was composed of dead epidermal cells, fibrin, and large numbers of PMNs. Healing occurred under the crust by migration of epidermal cells from the margins of the lesions and from the hair follicles. In organ culture, the lesion explants survived well, and reepithelialization even took place. Their excellent survival enabled us to compare the life spans of the infiltrating leukocytes within an inflammatory site. PMNs within the explants began disappearing during the first day of culture, and almost all had disappeared by 3 days. In contrast, over half of the basophils and the mononuclear cells within the explants were still present after 3 days of culture. The 1-, 2-, 3-, 6-, and 10-day (1.0-sq cm) SM lesion biopsies showed a 30-45% increase in weight (when compared with normal skin), presumably due to the extravasation of serum proteins and the fluids retained by them. When the biopsies were organ-cultured for 3 days, the 1-, 2-, and 3-day lesions lost weight, and the 6- and 10-day lesions (and normal skin) gained weight. These weight differences were not due to the amount of unbound protein extractable into the culture fluids, because both the early lesions and the late lesions contained about the same amount of unbound protein. The most likely explanation for these weight differences is that the newly formed ground substances of late lesions absorbed culture fluid, because the ground substance had changed from the sol state of acute inflammation (in which it was extractable) back to its normal gel state (in which it was not extractable). The unbound protein extractable into the culture fluids was mostly of serum origin. This protein averaged 1.9 mg for 1.0 sq cm normal skin explants (with a mean weight of 215 mg), and 6.4 mg for 1-day SM lesions (with a mean weight of 313 mg). Because rabbit serum contains about 60 mg protein/ml, these figures indicate that normal skin contained about 15% (unbound) serum by weight.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Inflammatory mediators and modulators release in organ culture from rabbit skin lesions produced in vivo by sulfur mustard. II. Evans blue dye experiments that determined the rates of entry and turnover of serum protein in developing and healing lesions.

Extravasated serum seems to be the major modulator of the local inflammatory response, because it provides both proinflammatory and antiinflammatory components. This report describes the rates of entry and turnover of extravasated serum protein in dermal inflammatory lesions produced by the military vesicant sulfur mustard (SM). Rabbits, bearing SM skin lesions, were given an intravenous injection of Evans blue dye, so that at the time of sacrifice, 2 hours later, their skin lesions were 2 hours and 1,2,3,6, and 10 days of age. Evans blue labels serum albumin, a representative serum protein. By multiplying the amount of Evans blue contained in the lesions by a factor that converted micrograms of Evans blue into milligrams of serum protein, the authors could estimate the 2-hour rate of entry of serum protein into these lesions. Serum protein in the lesions was both bound and unbound. The unbound protein was extractable from the lesions into the culture fluids, and, electrophoretically, was similar in composition to serum protein. Grossly edematous peak lesions (1 day of age) contained 7.8 mg of unbound serum protein per square centimeter of skin. Healing lesions (6 and 10 days of age) contained about 4.5 mg/sq cm, and normal skin about 1.7 mg/sq cm. Lesions 1 day of age had the highest rate of serum albumin entry, and about 36% of this Evans-blue-labeled protein was unbound, ie, extractable into the culture fluids. Lesions 3 and 6 days of age had a rate of serum albumin entry that was roughly half that of 1-day lesions, and only about 13% of this entering protein was unbound. Normal skin had a very low rate of serum albumin entry, and only 8% of this entering protein was unbound. The turnover rate of the unbound (extractable) serum protein could be estimated from the 2-hour entry rate of the Evans-blue-labeled albumin and the total protein in the culture fluids. In 1-day lesions, about 25% of the serum protein in the culture fluids was protein which had entered during the last 2 hours, so that 100% of this unbound protein should have been replaced once in 8 hours. In contrast, in 3- and 6-day lesions, this unbound serum protein should have been replaced once in about 35 hours, and in normal skin once in 80 hours. Evans-blue-labeled serum albumin continuously entered both the bound and unbound compartments of the SM lesions, even during the healing stages.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

[Documentation of mucous membrane changes in military gas (Lost) exposed patients].

Poison gases, such as "Lost" (bichloroethyl sulfide), which have been known since the first World war, and the use of mycotoxins can cause extremely grave alterations of the texture of the upper breathing and digestive system. These alterations are shown by photographs of three persons, and therapeutical measures are documented in a successive space of time. The significance of an early tracheotomy for a successful treatment is also mentioned.

Burns, Chemical↗
PubMed1985

The protective effect of different drugs in rats poisoned by sulfur and nitrogen mustards.

Based on the recent pathognomic accomplishment in the mechanisms of toxic actions, the favorable degree of protection was achieved by several drugs in acute poisoning of rats with sulfur and nitrogen mustards. It has been established that dexamethasone, promethazine, vitamin E, heparin, and sodium thiosulfate (a) prolonged the survival time in animals poisoned by 3 LD50s of toxic agents, (b) diminished the lethalty (with the protective indices ranging from 1.5 to 2.7), (c) antagonized the decrease of body weight, and (d) lessened the degree of pathological organ changes. The simultaneous administration of two or three of the drugs mentioned, of which sodium thiosulfate as chemical inactivator of the toxic agents was basic and consonant component, led to the further increase in effectiveness. It is concluded that satisfactory results obtained in this study speak in favor of the basic pathological effects of mustard gases, as well as possible causes and their possible ways of action as postulated by Dannenberg (1983).

Animals↗