Sulfur mustards systemic effects

Emad A, Rezaian GR The diversity of the effects of sulfur mustard gas inhalation on respiratory system 10 years after a single, heavy exposure. Analysis of 197 cases. Chest 112(3) 734-738, 1997... 

Mustard gas (H)—also known as yellow cross, yperite, sulfur mustard, Schwefellost, bis(2-chloroethyl) sulfide, and dichlor-diethylsulfide—is a chemical-warfare agent with both vesicant and systemic effects. H is colorless and almost odorless and is an oily liquid at 14-215°C with a molecular weight of 159.08. Except in extremely cold weather, the low vapor pressure (0.072 mm Hg at 20°C) and low volatility of H are sufficient to make contaminated surfaces a source of danger to anyone nearby. H is slightly soluble... 

Sulfur mustard is a known human carcinogen, and some of its degradation products may also be carcinogenic (IOM, 1993). Sulfur mustard acts as a vesicant or blister agent and shows acute systemic toxicity in addition to its effects on skin, eyes, and the respiratory tract. 

The skin and eyes are especially sensitive to the toxic effects of sulfur mustard. When applied to human skin, about 80% of the dose evaporates and 20% is absorbed (Vogt et al., 1984). About 12% of the amount absorbed remains at the site and the remainder is distributed systemically (Renshaw, 1946). Doses up to 50 pg/ cm cause erythema, edema, and sometimes small vesicles. Doses of 50-150 pg/cm cause bullous-type vesicles, and larger doses cause necrosis and ulceration with peripheral vesication. Droplets of liquid sulfur mustard containing as little as 0.0025 mg may cause erythema (Ward et al., 1966). Eczematous sensitization reactions were reported in several early studies and may occur at concentrations below those causing direct primary irritation (Rosenblatt et al., 1975). In humans, the LCtso (estimated concentration x exposure period lethal to 50% of exposed individuals) for skin exposures is 10,000 mg-min/m (DA, 1974) (for masked personnel however, the amount of body surface area exposed was not reported). The ICt 50 (estimated concentration x exposure period incapacitating to 50% of exposed individuals) for skin exposures is 2000 mg-min/m at 70-80°F in a humid enviromnent and 1000 mg-min/m at 90°F in a dry enviromnent (DA, 1974, 1992). The ICtso for contact with the eyes is 200 mg-min/m (DA, 1974, 1992). The LDl for skin exposure is 64 mg/kg and the LD50 is estimated to be about 100 mg/kg (DA, 1974,1992). 

Studies in animals have shown that sulfur mustard may induee developmental and reproductive effects (reviewed in NRC, 1999, 2003). Acute exposures resulting in systemic uptake may have effects on reproductive organs, including inhibition of spermatogenesis. Fetal anomalies were observed in tests with rats given sulfur mustard during gestation but only at maternally toxic doses. 

Jafari, M. (2007). Dose- and time-dependent effects of sulfur mustard on antioxidant system in liver and brain of rat. Toxicology 231 30-9. 

Obviously, these findings confirm the theoretical assumption that the lipophilic properties of sulfur mustard result in a distribution, primarily in lipophilic tissues. High concentrations found in the brain may also explain why the central nervous system is one of the organs exhibiting systemic effects of sulfur mustard poisoning, even though it is not a site of rapidly proliferating cells. 

Hobson, D., Blank, J., Menton, R. (1985). Comparison of effectiveness of 39 experimental decontamination systems and evaluation of the effect of three pretreatment materials against percutaneous application of soman, thickened soman, VX, and sulfur mustard to the rabbit. Aberdeen Proving Ground, MD. MREF Task 85-12. 

Toxic effects of sulfur mustard and ethyleneimine on animals were described in the 19th century. The powerful vesicant action of sulfur mustard led to its u.se in World War I. and medical examination of the victims revealed that tissues were damaged at sites distant from the area of contact." Such systemic elTects included leukopenia, bone marrow aplasia, lymphoid tissue suppression, and ulceration of the gastrointestinal tract. Sulfur mustard was shown to be active against animal tumors, but it was too nonspecific for clinical use. A variety of nitrogen mustards were synthesized between the two world wars. Some of these compounds (e.g.. 

Ocular, percutaneous, inhalation, ingestion, and injection are all possible routes of exposure. Effects may be local, systemic, or both. All of the nitrogen mustards are oily liquids that are colorless to pale yellow and evaporate slowly. They are more dangerous than sulfur mustard but, like sulfur mustard, they are derivatives of ammonia. The most toxic and most volatile of the three nitrogen mustards is HN-2, but HN-3 is used more because it is stable. 

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. 

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