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stimulation of hair growth, and cutaneous sensitization (Turanow et al., 1977). Long-term effects are yet to be reported.

Experimental Exposure

Renshaw (1946) has reported on the development of contact sensitivity in man following localized exposure to liquid sulfur mustard. Cutaneous sensitivity may be seen within 8 days following the first application, and a more pronounced effect is seen after four weeks. The incidence of hypersensitivity varies between 30 and 65 percent of exposed individuals. Sensitivity may be immediate (urticaria) or delayed (dermatitis) and appears to last for a lifetime. Sensitivity also includes flares of old, healed sulfur mustard injured sites after a fresh application of sulfur mustard to normal unaffected skin.

EVIDENCE OF LONG-TERM HEALTH EFFECTS OF LEWISITE

The long-term health effects of Lewisite on skin are unknown. There is an extensive bibliography on the long-term effects of arsenicals on specific organ systems, but with few exceptions the skin is omitted from these studies. There is considerable controversy over which arsenicals are most toxic to human and animal tissues (e.g., inorganic arsenicals versus organic arsenicals, versus trivalent, versus pentavalent). The more recent literature leans toward the conclusion that most long-term effects attributable to arsenicals are due to exposure to inorganic trivalent arsenic (Goldman and Dacre, 1989; Squibb and Fowler, 1983).

Epidemiologic studies have clearly demonstrated a real association between chronic adverse reactions and occupational exposure to inorganic arsenic in pesticides, herbicides, fungicides, and animal disinfectants, and in smelter workers. In medicine, preparations such as Fowler's solution, asiatic pills, and Donovan's solution that contain trivalent elemental arsenic have been associated with long-term effects including dermatitis, hyperpigmentation, loss of hair, disseminated cutaneous keratoses, palmar hyperkeratosis, and cutaneous cancer, including basal cell, squamous cell, and Bowen's intraepidermal squamous cell cancer. Yet the long-term administration of organic arsenicals in the treatment of syphilis, trypanosomal diseases, parasitic infestations, relapsing fever, and yaws has not been associated with any of the adverse reactions outlined above.

Animal Studies and Cellular Bioassays

Most animal studies of the long-term effects of Lewisite and other arsenicals on skin and other organs have been directed toward the



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