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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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