Sulfur mustards skin lesions

Zlotogorski, A., Goldenhersh, M., Shafran, A., 1997. A model for quantitative measurement of sulfur mustard skin lesions in the rabbit ear. Toxicology 120, 105-110. 

Reid, F.M., Niemuth, N.A., Shumaker, S.M., Waugh, J.A., Graham, J.S. (2007). Biomechanical monitoring of cutaneous sulfur mustard-induced lesions in the weanling pig model for depth of injury. Skin Res. Technol. 13(2) 217-25. 

Hobson and Snider (1992) evaluated the effectiveness of hypochlorite solutions in decontaminating rabbit intact skin and wounds exposed to VX or sulfur mustard. When the intact skin was decontaminated with bleach at 5% or 0.5% hypochlorite concentrations 1 min after sulfur mustard exposure, lesion areas were reduced by 4.6- and 4.3-fold, respectively. For VX-contaminated intact skin, 5% and 0.5% sodium hypochlorite increased the median lethal dose of VX by 19- and 16-fold, respectively. The results indicate that 0.5 % bleach is as effective as 5 % in decontaminating sulfur mustard and VX on intact skin. However, when VX was applied to a wound site, the 0.5% bleach was not effective in increasing survival rate, whereas 5% bleach increased the median lethal dose 2-fold. 

Dermal (skin) contact with sulfur mustard agents causes erythema and lesions (blistering), while contact with vapor may result in first and second degree burns contact with liquid typically produces second and third degree chemical burns. Any burn area covering 25 percent or more of the body surface area may be fatal. Respiratory contact is a dose-related factor in the sense that inflammatory reactions in the upper and lower airway begin to develop several hours after exposure and progress over several days. 

Vogt, R.F., Dannenberg, A.M., Jr., Schofield, B.H., and Papirmeister, B. Pathogenesis of skin lesions caused by sulfur mustard. Fundamental and Applied Toxicology, in press. 

The study by McNamara et al. (1975) was an inhalation study using rats, mice, rabbits, guinea pigs, and dogs therefore, equivalent oral doses could only be estimated from the data. Because of that, the subcommittee considered the study to be inappropriate for deriving the RfD for sulfur mustard. Furthermore, inhalation of sulfur mustard resulted in lesions to the skin and eyes, which would not be expected from oral exposure. The subcommittee also reviewed the Institute of Medicine s (lOM 1993) evaluation of the health effects of mustard gas and found no other relevant studies with respect to derivation of the RfD. 

Higuchi, K., Kajiki, A., Nakamura, M., Harada, S., Pula, P.J., Scott, A.L., Dannenberg, A.M., Jr. (1988). Proteases released in organ culture by acute dermal inflammatory lesions produced in vivo in rabbit skin by sulfur mustard hydrolysis of synthetic peptide substrates for trypsin-like and chymotrypsin-like enzymes. Inflammation 12 311-34. 

Tanaka, F., Dannenherg, A.M., Jr. et al. (1997). Chemotactic factors released in culture by intact developing and healing skin lesions produced in rabbits by the irritant sulfur mustard. Inflammation 21 251-67. 

Wormser, U., Brodsky, B., Proscura, E., Foley, J.F., Jones, T., Nyska, A. (2005). Involvement of tumor necrosis factor-alpha in sulfur mustard-induced skin lesion effect of topical iodine. Arch. Toxicol. 19 660-70. 

There may be no skin lesions following mild vapor exposures. However, severe vapor or liquid exposure to nitrogen mustard will produce effects similar to those of sulfur mustard (but the onset is sooner than with sulfur mustard). These effects include erythema, irritation, and itching, with blisters developing in the erythematous areas. 

The second exception is that while an antidote is available for systemic effects of Lewisite exposure, there are no antidotes for nitrogen mustard or sulfur mustard toxicity, with one minor caveat if given within minutes after exposure, intravenous sodium thiosulfate may prevent death due to sulfur mustard exposure (25). Otherwise, the medical management for skin, ocular, and respiratory exposure is only supportive. One guideline physicians can follow is to keep skin, eye, and airway lesions free from infection. 

Wormser, U., Brodsky, B., Green, B.S., Arad-Yellin, R., and Nyska, A. (1997). Protective effect of povidone-iodine ointment against skin lesions induced by sulfur mustards and by non-mustards vesicants. Arch Toxicol 71, 165-70. 

Chemical warfare agents were not used in World War n, although both sides had the capability. Reports have surfaced that chemical agents were used in experiments conducted on concentration camp prisoners, by both the Third Reich and Japan. An accidental exposure to mustard did occur during World War II when a tanker was sunk and mustard leaked and contaminated the waters of an Italian port. Survivors rescued from the sinking ship developed classic skin lesions associated with sulfur mustard. 

According to Klehr (1984), German workers involved in the dismantling of a sulfur mustard facility developed multiple skin lesions including basal cell carcinomas, Bowen s disease, and carcinoma spinocellulare (a histological characterization of an epidermal carcinoma). The incidence rate for all tumors, including skin tumors, was 34% in 53 workers evaluated. 

Tanaka, F., Dannenberg, A. M., Jr., Higuchi, K., Nakamura, M., Pula, P. J., Hugli, T. E., Discipio, R. G., and Kreutzer, D. L. (1997) Chemotactic factors released in culture by intact feveloping and healing skin lesions produced in rabbits by the irritant sulfur mustard. Inflammation 21, 251-267. (Abstract)... 

Studies with sulfur mustard [SM], a chemical warfare vesicant causing debilitating skin lesions, have shown an increase in the immune response. However, the contribution of this response to lesion pathogenesis is not clear. 

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