Sulfur mustards occupational exposures

Various standards and guidelines have been developed for sulfur mustard. These values are applieable to occupational exposures, emergeney planning and response efforts, and remediation efforts. Airborne exposure limits (AELs) and health-based environmental sereening levels (HBESLs) for sulfur mustard have been developed by the US Army (USACHPPM, 1999, 2000). Most health-based criteria for sulfur mustard vapor exposure are based upon protection of the eyes and respiratory traet whieh are the most sensitive targets. 

USACHPPM (US Army Center for Health Promotion and Preventive Medicine) (2000). Evaluation of airborne exposure limits for sulfur mustard occupational and general population exposure criteria. Aberdeen Proving Ground, MD. Technical Report 47-EM-3767-00. 

To ensure that chemical contamination is rednced to safe concentrations at stockpile and NSCM sites before they are used for residential, occupational, or wildlife purposes, the U.S. Army requested that health-based exposure limits for GA, GB, GD, VX, sulfur mustard, and lewisite be developed to protect the pnblic and the environment. Oak Ridge National Laboratory (ORNL) was asked to conduct the health risk assessments and propose chronic oral reference doses (RfDs) and, where... 

The studies of Nishimoto et al. (1988), Yamada (1974) and Inada et al., (1978) provide strong evidence for a causal link between chemical agent exposure and cancer however, because the workers were exposed to multiple chemicals, it is not possible to state conclusively that the cancers were due solely to sulfur mustard. Furthermore, it should be noted that several possible confounding factors, such as tobacco smoking habits, preexisting health conditions, and post-exposure occupational histories of the workers, were not evaluated. In addition, SMRs themselves may not provide an accurate estimate of relative cancer risk if they do not correlate with tumor incidence rates in exposed and control groups (i.e., if social/economic or other differences between control and exposed groups result in differences in health care which affect survival rates). 

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. 

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. 

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. 

Sulfur mustard is rated by the International Agency for Research on Cancer (lARC) as a human carcinogen and is a known risk factor for occupational lung cancer (Nishimoto et al., 1987 Ghanei and Vosoghi, 2002). Zafarghandi et al. (2012) described the incidence of cancer in 7,570 Iranian sulfur mustard-exposed veterans compared to 7,595 unexposed subjects in a 25-year follow-up study. Cancer incidence was significantly increased with exposure to sulfur mustard. The incidence rate ratio for cancer was 1.81 (95% Cl 1.15-2.34) however, no increased risk of site-specific cancers were found. The hazard ratio of cancer occurrence was 2.02 (95% Cl 1.41-2.88). 

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