lewisite and Respiratory-Tract-Diseases

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.

Topics: Animals; Arsenic Poisoning; Arsenicals; Cell Membrane Permeability; Chemical Warfare; Dermatitis, Irritant; DNA Damage; Female; Humans; Irritants; Keratitis; Lethal Dose 50; Lung Neoplasms; Male; Mustard Gas; Mutation; Pregnancy; Reproduction; Respiratory Tract Diseases

First used in World War I, chemical blistering agents present a serious medical threat that has stimulated renewed interest in the light of extensive use in recent conflicts. Current medical management cannot yet prevent or minimize injury from the principal agent of concern--sulfur mustard. Research directed at this goal depends on defining effective intervention in the metabolic alterations induced by exposure to sulfur mustard.

Topics: Arsenic Poisoning; Arsenicals; Chemical Warfare; Decontamination; Eye Diseases; Humans; Mustard Gas; Respiratory Tract Diseases; Skin Diseases

Health and exposure criteria have not been established for lewisite [dichloro(2-chlorovinyl)arsine], a potent toxic vesicant that reacts with the sulfhydryl groups of proteins through its arsenic group. Sixty Sprague-Dawley rats of each sex, 6-7 wk old, were divided into 6 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 d/wk for 13 wk. 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 platelets 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 glandular 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 respiratory tract, possibly from deposition 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.

Topics: Animals; Arsenic Poisoning; Arsenicals; Blood Cell Count; Body Weight; Chemical Warfare Agents; Female; Liver Function Tests; Male; No-Observed-Adverse-Effect Level; Rats; Rats, Sprague-Dawley; Respiratory Tract Diseases; Stomach; Stomach Ulcer; Toxicity Tests