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intractable conjunctivitis. Evidence in laboratory animals indicates no causal relation between exposure to Lewisite and any long-term ocular disease process. However, any corneal scarring or vascularization that occurs soon after injury from Lewisite will persist.

There is an extensive base of knowledge from studies in laboratory animals and humans regarding the long-term effects of mustard agents on the eye. Thus, acute, severe injury of the eye with sulfur mustard, resulting in corneal scarring among other effects, can result in recurrent corneal ulcerative disease. The maximum incidence of this disease occurs 15 to 20 years after the injury. Acute severe injury from sulfur mustard has also been shown to result in the development of delayed recurrent keratitis and corneal opacities. The conjunctiva of the eye has been shown to be more vulnerable than the cornea to sulfur mustard exposure, explaining the development of intractable, prolonged conjunctivitis even in the absence of severe injury to the cornea.

The evidence indicates a causal relation between acute, severe exposure to mustard agents and increased skin pigmentation and depigmentation, chronic skin ulceration, scar formation, and the development of cancer in human skin. A causal relationship also exists between chronic exposure to minimally toxic, and even subtoxic, doses and skin pigmentation abnormalities and cutaneous cancer. There is insufficient evidence, however, to establish a causal relationship between Lewisite exposure and long-term adverse effects on skin.

There has been much research on the toxic mechanisms of acute skin injury from mustard agents, especially in laboratory animals and tissue cultures. Injuries from  mustard agents have been shown in these models to result in a complex cascade of biochemical reactions that cause cell death and genotoxicity. Studies of carcinogenesis were positive in laboratory animals, but these studies employed outdated methods and are relatively crude by today's standards. Studies in humans after battlefield or occupational exposure also vary tremendously in quality.

Nevertheless, skin cancers have been observed in many of these studies. That fact, coupled with documented and plausible biological mechanisms, indicates cancer as a likely consequence of acute, severe (or chronic, mild to moderate) mustard agent injury to the skin. Scar formation and chronic ulceration of the skin following mustard agent exposure have been well documented in the literature. Genital regions are especially sensitive to exposure, and scarring of the scrotum and penis can seriously impair sexual performance and capability. In those studies in which pigmentation abnormalities were reported, including recent observations in casualties of the Iran-Iraq war, the abnormalities



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