Mustard Gas as a Cause of Respiratory Neoplasia in Man

Wada, Sunao; Miyanishi, Michihiro; Nishimoto, Yukio; S, Kambe; Miller, RobertW.

doi:10.1016/s0140-6736(68)91863-1

Cited by 165 publications

(45 citation statements)

References 4 publications

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“…German workers exposed to sulfur and nitrogen mustard during the dismantling of a chemical warfare agent factory have experienced subsequent (latent period, if any, unspecified) skin tumors and necrotic skin ulcerations that spread and were resistant to therapy (64). A high proportion of the Japanese factory workers also had a productive cough, irregular fevers, longstanding chronic bronchitis, emphysematous changes, and pleural adhesions (58,65). A study of 156 death certificates from former workers in the Japanese weapons factory noted that 54% died ofrespiratory diseases (58).…”

Section: Agents H/hdmentioning

confidence: 99%

Toxicity of vesicant agents scheduled for destruction by the Chemical Stockpile Disposal Program.

Watson

Griffin

1992

Environ Health Perspect

105

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The vesicant agents of the unitary chemical munitions stockpile include various formulations of sulfur mustard [bis-(2-chloroethyl) sulfide; agents H, HD, and HT] and small quantities of the organic arsenical Lewisite [dichloro(2-chlorovinyl) arsine; agent L]. These agents can be dispersed in liquid, aerosol, or vapor form and are capable of producing severe chemical burns upon direct contact with tissue. Moist tissues such as the eyes, respiratory tract, and axillary areas are particularly affected. Available data summarizing acute dose response in humans and laboratory animals are summarized. Vesicant agents are also capable of generating delayed effects such as chronic bronchitis, carcinogenesis, or keratitis/keratopathy of the eye under appropriate conditions of exposure and dose. These effects may not become manifest until years following exposure. Risk analysis derived from carcinogenesis data indicates that sulfur mustard possesses a carcinogenic potency similar to that of benzo[a]pyrene. Because mustard agents are alkylating compounds, they destroy individual cells by reaction with cellular proteins, enzymes, RNA, and DNA. Once begun, tissue reaction is irreversible. Mustard agents are mutagenic; data for cellular and laboratory animal assays are presented. Reproductive effects have not been demonstrated in the offspring of laboratory rats. Acute Lewisite exposure has been implicated in cases of Bowen's disease, an intraepidermal squamous cell carcinoma. Lewisite is not known to generate reproductive or teratogenic effects.

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Section: Agents H/hdmentioning

confidence: 99%

Toxicity of vesicant agents scheduled for destruction by the Chemical Stockpile Disposal Program.

Watson

Griffin

1992

Environ Health Perspect

105

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“…Based on one incidence of accidental exposure to a soldier's leg, Lewisite is considered a suspect carcinogen in man (Krause and Grussendorf, 1978). Workers of a Japanese factory producing mustard and Lewisite agents during World War II had a high mortality rate due to respiratory and gastrointestinal cancers (Wada et al, 1968;Yamakido et al, 1985). These workers were potentially exposed to unknown quantities of both sulfur mustard and Lewisite; therefore, it is not possible to implicate Lewisite as a carcinogen because of possible confounding effects of the carcinogen, sulfur mustard.…”

Section: Introductionmentioning

confidence: 99%

Toxicology Studies on Lewisite and Sulfur Mustard Agents: Subchronic Toxicity Study of Lewisite in Rats Final Report

Sasser¹,

Cushing²,

Kalkwarf³

et al. 1989

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Occupational health standards have not been established for arsine], a potent toxic vesicant wh1ch reacts with the sulfhydryl groups of proteins through its arsenic group. Sixty Sprague-Dawley rats of each sex, 6-7 weeks old, were divided into six groups (10/group/sex) and gavaged with either, 0, 0.01, 0.1, 0.5, 1.0 or 2.0 mg/kg of Lewisite in sesame oil 5 days/week for 13 weeks. No significant dose-related change in body weight was observed. At the high dose serum protein, creatinine, SGOT, and SGPT were decreased in males; lymphocytes and platlets were increased in females. A treatment-related lesion was detected in the forestomach of both sexes at 2.0 mg/kg. These lesions were characterized by necrosis of the stratified squamous epithelium accompanied by infiltration of neutrophils and macrophages, proliferation of neocapillaries, hemorrhage, edema and fibroblast proliferation. Mild acute inflammation of the gradular stomach was also observed in some cases at 1.0 and 2.0 mg/kg. Early deaths were attributed to severe inflammation of the upper and/or lower tract ibl from tion or reflux of test material into the pharynx. Estimated dose range for NOEL appears to be >0.5 and <1.0 mg/kg when administered orally.

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“…Given that mustard is relatively persistent, such observations are significant from a wartime perspective in that people exposed to prolonged off-gassing of mustard-contaminated material or terrain could develop chronic respiratory problems. Occupational exposures have also underscored the carcinogenic and mutagenic potential of mustard in humans (40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50).…”

Section: Ch2-ch2-ci S Ch2-ch2-cimentioning

confidence: 99%

Hazards of chemical weapons release during war: new perspectives.

Reutter

1999

Environ Health Perspect

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The two major threat classes of chemical weapons are mustard gas and the nerve agents, and this has not changed in over 50 years. Both types are commonly called gases, but they are actually liquids that are not re ly voatile. These agents were designed specifically to harm people by any route of exposure and to be effective at low doses. Mustard gas was used in World War I, and the nerve agents were developed shortly before, during, and after World War II. Our perception of the potency of chemical weapons has changed, as well as our concern over potential effects of prolonged exposures to low doses and potential target populations that indude women and cildren. Many of the toxicologic studies and human toxicity esmates for both mustard and nerve agents were designed for the purpose of quickly developing maximal casualties in the least sensitive male soldier. The 'toxcity" of the chemical weapons has not changed, but our perception of 'toxicity" has.

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Mustard Gas as a Cause of Respiratory Neoplasia in Man

Cited by 165 publications

References 4 publications

Toxicity of vesicant agents scheduled for destruction by the Chemical Stockpile Disposal Program.

Toxicity of vesicant agents scheduled for destruction by the Chemical Stockpile Disposal Program.

Toxicology Studies on Lewisite and Sulfur Mustard Agents: Subchronic Toxicity Study of Lewisite in Rats Final Report

Hazards of chemical weapons release during war: new perspectives.

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