Characterization of the Sulfur Mustard Vapor Induced Cutaneous Lesions on Hairless Guinea Pigs

The identification of antivesicant compounds has been hindered by the lack of a suitable in vivo model. Our laboratory has been evaluating the hairless guinea pig as a useful animal model to mimic the human cutaneous response to sulfur mustard (HD) exposure. The characterization of two cutaneous responses to HD, quantification of erythema using a reflectance color meter, and pathology by light microscopy, is described in this manuscript. Fifty-two hairless guinea pigs were exposed to saturated HD vapor using a vapor cup technique. The dose response of HD vapor was established by varying the duration (2-11 min) of skin exposure to an HD vapor concentration of 0.77 g/m3 under occluded caps. The degree of erythema was determined by measuring the increase in the reflectance meter's a (relative parameter measuring the degree of redness) response for each exposure site at 4, 5, 6, and 24-h postexposure. A linear increase in erythema was observed between the 2- and 4-min HD exposure doses for each post HD observation. The increase in erythema reached a maximum with the 5-min HD exposure dose. HD exposures between 5 and 11 min produced the same degree of erythema. The second method of evaluation-degree of lesion pathology-was determined by observing the percent incidence (percentage of exposure sites with positive response) of several parameters, including (in order of increasing dose dependence) intracellular edema, basal cell necrosis, pustular epidermitis, microblister formation, and follicular necrosis. All markers exhibited a linear dose-response curve with parallel slopes. The more extensive cellular damage occurred at longer exposure times. We have observed in the hairless guinea pig microblister formation at the dermal-epidermal junction similar to that reported in other animal models including humans. The linear dose-response curve for microblister formation correlated highly with available historical data for fluid-filled blisters in humans under similar exposure conditions.