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Veterans at Risk: The Health Effects of Mustard Gas and Lewisite (1993)
Institute of Medicine (IOM)

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. "7 Nonmalignant Respiratory Effects of Mustard Agents and Lewisite." Veterans at Risk: The Health Effects of Mustard Gas and Lewisite. Washington, DC: The National Academies Press, 1993.

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Veterans at Risk: The Health Effects of Mustard Gas and Lewisite

edema, has also been reported to be a prominent finding following inhalation of Lewisite (Urbanetti, 1988).

EVIDENCE OF LONG-TERM HEALTH EFFECTS

Animal Studies

Inhaled sulfur mustard vapor produces destruction of the epithelium of the respiratory tract. Apparently, much of the vapor is removed higher in the respiratory tract: the nasal, laryngeal, and tracheobronchial regions appear to be the most severely affected (Papirmeister et al., 1991). Many of the animal studies of toxicity from inhaled sulfur mustard were conducted during WWI. In rabbits, inhalation of sulfur mustard produced damage that was particularly prominent in the upper respiratory tract, including the nasal passages, pharynx, larynx, trachea, and large bronchi (Warthin and Weller, 1919). The damage increased with increasing exposure concentrations. Low levels of exposure caused congestion of these areas without hemorrhage. Degeneration of mucous cells was observed in the pharynx and larynx. The highest levels of exposure caused necrosis of the epithelium, infiltration of white blood cells, and the formation of diphtheritic-like pseudomembranes.

Experiments in dogs showed necrosis of the epithelium of the upper respiratory passages with pseudomembrane formation. This usually extended to the bronchioles. Animals that died from two to ten days following exposure had evidence of necrotizing pneumonia. Animals sacrificed at later times showed localized ulceration or constriction of the trachea (Winternitz, 1919).

Lung damage also occurred following intravenous injection of sulfur mustard into animals (Office of Scientific Research and Development, 1946). Intravenous injection of a solution of sulfur mustard in either propylene glycol or thiodiglycol was reported to cause diffuse pulmonary congestion and edema, but pure sulfur mustard given rapidly caused more serious necrotic and hemorrhagic lesions of the lung. However, these authors attributed this lung damage from injected sulfur mustard to localization of particulate sulfur mustard in the pulmonary capillaries, because pulmonary injury was not observed with other parenteral routes of administration.

Sulfur mustard is absorbed through the skin into the systemic circulation. Following intravenous administration of radiolabeled sulfur mustard in rabbits, the level of radioactivity in tissue was highest in kidney, followed by lung and then liver (Boursnell et al., 1946). Thus, it is conceivable that some sulfur mustard exposure of respiratory tract tissue with subsequent biological effects could occur following systemic absorption from skin exposure.

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Front Matter (R1-R20)
Executive Summary (1-8)
1 Introduction (9-13)
2 Methods of Literature Collection and Survey (14-20)
3 History and Analysis of Mustard Agent and Lewisite Research Programs in the United States (21-60)
4 Findings from the Public Hearing Process (61-70)
5 Chemistry of Sulfur Mustard and Lewisite (71-80)
6 Relationship of Mustard Agent and Lewisite Exposure to Carcinogenesis (81-111)
7 Nonmalignant Respiratory Effects of Mustard Agents and Lewisite (112-130)
8 Ocular Effects of Mustard Agents and Lewisite (131-147)
9 Dermatological Effects of Mustard Agents and Lewisite (148-178)
10 Other Physiological Effects of Mustard Agents and Lewisite (179-198)
11 Relationship of Mustard Agent and Lewisite Exposure to Psychological Dysfunction (199-213)
12 Summary of Findings and Recommendations (214-226)
Bibliography (227-330)
A. Scientific and Background Presentations Made to the Committee (331-334)
B. Excerpt from The Residual Effects of Warfare Gases (335-337)
C. Involvement of the National Academy of Sciences Complex in World War II Research Programs: A Summary (338-339)
D. Excerpts from Chamber Tests with Human Subjects I, II, and IX. Naval Research Laboratory Reports Nos. P-2208 and P-2579 (340-369)
E. Interim Report and Addendum: Feasibility of Developing a Cohort of Veterans Exposed to Mustard Gas During WWII Testing Programs (370-377)
F. Summary of the Department of the Army Report: Use of Volunteers in Chemical Agent Research (378-381)
G. Public Hearing Announcement (382-385)
H. Letter from Dr. Jay Katz to Dr. David P. Rall (386-389)
I. Risk Assessment Considerations for Sulfur Mustard (390-398)
J. Examination of the Effects of Certain Acute Environmental Exposures on Future Respiratory Health Consequences (399-416)
List of Acronyms and Abbreviations (417-420)
Index (421-428)