Sulfur mustard acute toxicity

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. 

Information on the acute oral toxicity of sulfur mustard is quite limited. The oral LDl, for humans has been estimated to be 0.7 mg/kg (DA, 1992). The oral LD50 for rats is 17 mg/kg (DA, 1974). Rats treated with 2.5 mg/ kg/day for 14 days developed inflammation, petechial hemorrhage, thickening, and sloughing of the gastric mucosa (Hackett et al., 1987). 

Wulf et al. (1985) reported significant (p<0.001) increases in sister chromatid exchanges in lymphocytes of eleven fisherman who had accidently been exposed to sulfur mustard in sufficiently high concentrations to canse signs of acute toxicity. 

In addition to the acute toxic effects on the eyes, skin, and respiratory tract, both acute and longer-term neuropsychiatric effects (e.g. depression, anxiety, neurasthenia, insomnia, post-traumatic stress syndrome) have been documented for individuals exposed to sulfur mustard (Romano et al, 2008). Many of these effects have been documented for individuals exposed during noncombat (e.g. munitions plant workers) activities and are not always the result of high-level exposure that result in serious overt effects. Longer-term effects such as chronic bronchitis have been associated with occupational exposures that included episodes of acute toxicity, and delayed or recurrent keratitis may occur 8-40 years after a severe vapor exposure. Sulfur mustard-induced immunosuppression resulting in greater susceptibility to infections has also been reported. 

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. 

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. 

Studies of occupational exposures to sulfur mustard indicate an elevated risk of respiratory tract and skin tumors following long-term exposure to acutely toxic concentrations. Overall, several factors are important regarding the assessment of the carcinogenicity of sulfur mustard. Increased cancer incidence in humans appears to be associated only with exposures that caused severe acute effects, and occupational exposures tended to involve repeated exposures and repeated injury of the same tissues. Because the therapeutic use of the sulfur mustard analog nitrogen mustard is associated with an increased incidence of CML, the reports of CML in HD-exposed individuals appear to be relevant to the eareinogenicity of sulfur mustard. 

In addressing the ecotoxicological implications of HD dumped in the Baltic Sea, Muribi (1997) reported on the acute toxicity of HD to the invertebrate Daphnia magna in brackish water at 19.5°C. Exposure to 0.5 mg/1 HD (the highest concentration tested) for 48 h did not induce any visible effects. Additional toxicity studies with salt- and freshwater organisms, reviewed by Muribi (1997) and Munro et al. (1999), indicate that dissolved sulfur mustard is generally not acutely toxic at concentrations below 1 mg/1 (close to its water solubility value). For some algae, a concentration of 1 mg/1 may be acutely toxic (Stock, 1996). Thus, the environmental action of HD is limited by its low water solubility. 

Delayed Toxicity. Acute exposures to sulfur mustard can also result in longterm respiratory damage manifested as asthma-like conditions, emphysematous... 

Anderson, D.R., Yourick, J.J., Moeller, R.B., et al., 1996. Pathologic changes in rat lungs following acute sulfur mustard inhalation. Inhal. Toxicol. 8, 285-297. Anzueto, A., Delemos, R.A., Seidenfeld, J., et al., 1990. Acute inhalation toxicity of soman and sarin in baboons. Fund. Appl. Toxicol. 14, 676-687. 

A total of 29.8 5.31 ig sulfur mustard per animal was absorbed, 90% of which remained in the skin. This result agrees with an in vitro study by Hattersley et al. (2008) using human skin samples, which confirmed that a depot of sulfur mustard existed for at least 24 h following dermal exposure, and estimated concentrations in skin is at least 20 times above the acutely toxic concentration. 

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