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injury caused by a variety of toxic chemicals, and mechanical devices. Unsophisticated and untrained observations of sulfur mustard skin injury have often led to distorted accounts of such injuries. Any interpretations of published and unpublished data should be made based on a knowledge of normal and abnormal morphologic, biochemical, and physiological responses of normal and injured human skin.

ACUTE EFFECTS AND BIOLOGICAL MECHANISMS

Sulfur Mustard

Sulfur mustard is an oily substance that is freely soluble in animal oils, fats, and organic solvents (lipophilic). It is only slightly soluble in water, yet water is required for activation. When delivered as a liquid or vapor, the skin plays a very important role as a portal of entry for sulfur mustard. The lipophilic nature of sulfur mustard and the affinity of skin for lipophilic substances make the skin a fairly good transport system for this agent. After cutaneous exposure to sulfur mustard, high levels appear immediately, but transiently, within the skin. A portion of a given dose passes rapidly from the skin into the bloodstream to elicit toxicity at distant sites. However, even under the most ideal circumstances, only a very small portion, probably only 20 percent, of a single dose of sulfur mustard penetrates human skin (Cullumbine, 1947; Renshaw, 1946). Of this amount, about 12 percent reacts with components in the skin, principally within the epidermis. The remainder (about 8 percent) is absorbed systemically. At a temperature of 21°C, sulfur mustard rapidly penetrates human skin. Renshaw (1946) noted that sulfur mustard liquid or saturated vapor penetrates human skin at a rate of 1 to 4 mg/cm2/min at 21°C. Any increase in ambient temperature causes increased penetration.

There is substantial individual variation in the cutaneous response to sulfur mustard. In general, however, the effects of sulfur mustard on the skin depend on a number of factors including the dose of drug delivered, delivery medium (vapor or liquid), length of exposure of skin cells, degree of hydration of the skin, temperature of the atmosphere, thickness and surface area of the exposed skin, presence or absence of infection, and the intactness of exposed skin. Large dosages of sulfur mustard vapor delivered at 1,000-10,000 mg·min/m 3 (Ct), or liquid at 40-100 mg/cm2 over a long exposure time, will yield significant systemic toxicity, including death. Small vapor dosages at 50 Ct, or liquid at 10-20 mg/cm² and a short exposure time, yield limited local toxicity. Local toxicity is manifest not only in the skin, but also in the eye and mucous membrane of the respiratory tract.

The time of onset of visible cutaneous effects is related to dose and



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