Sulfur mustard lethal effects

Sulfur mustards (designated H [mustard], HD [distilled mustard], and HT [HD and T mixture]) do not present acute lethal hazards. Their principal effect is severe blistering of the skin and mucous membranes. Epidemiological evidence indicates a causal relationship between exposure to mustard agent at high concentrations and the development of chronic nonreversible respiratory disorders, such as chronic bronchitis and asthma, and ocular diseases, such as delayed recurrent keratitis and prolonged, intractable conjunctivitis (IOM, 1993). Sulfur mustard has been classified as a known human carcinogen based on evidence of in-... 

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). 

Several studies have also demonstrated that sulfur mustard causes dominant lethal mutations. Rozmiarek et al. (1973) reported a dominant lethal mutation rate of 9.4% ( 1.9%) in rats after adult males had been exposed to 0.1 mg HD/m for 12 weeks. Sasser et al. (1990) reported that a dominant lethal effect occurred after male Sprague-Dawley rats were dosed orally with 0.5 mg HD/kg/day 5 days/week for 10 weeks. The observed effects included increases in early fetal absorptions, preimplantation losses, and decreases in total live embryo implants. A significant increase in the percentage of abnormal sperm was also reported. Dominant lethal mutations, as well as chromosome rearrangements, have also been observed in Drosophila melanogaster exposed to sulfur mustard (Auerbach and Robson, 1946). 

Sasser L.B., R. A. Miller, J.A. Cushing and J.C. Dacre. 1990. Dominant lethal effect of sulfur mustard in rats. Toxicologist 10 225. (Abstract) Scott, D., M. Fox and B.W. Fox. 1974. The relationship between chromosomal aberrations, survival and DNA repair in tumor cell lines of differential sensitivity to x-rays and sulphur mustard. Mutat. Res. 22 207-221. 

Walker, l.G. and C.J. Thatcher. 1968. Lethal effects of sulfur mustard on dividing mammaUan cells. Radial. Res 34 110-127. 

Acute lethality data in animals are summarized in Table 8.7. Based upon the animal data, interspecies variability in the lethal response to sulfur mustard vapor is less than an order of magnitude. For nonlethal effects, the animal data suggest that test species exhibit signs of toxicity that are qualitatively similar to humans when acutely exposed to sulfur mustard vapor. Ocular and respiratory tract irritations are clearly evident in studies using dogs, rats, mice, rabbits, and guinea pigs. 

The genotoxicity of sulfur mustard is well documented. It is known to produce DNA cross-hnks, mutations following replication or repair errors, chromosomal breaks, and chromosomal aberrations. Occupational exposures have been associated with increased frequencies of somatic cell mutations, sister chromatid exchanges, and chromosome abnormalities. Studies with rats indicate that subchronic inhalation or oral exposures can produce dominant lethal effects. 

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. 

Sasser LB, Miller RA, Cushing JA, Dacre JC (1990) Dominant lethal effect of sulfur mustard in rats. Toxicologist 10 225 (abstr). 

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