Mustard carcinogenic effects

The work of Boyland and Horning,10 Heaton,26-2 and others stimulated interest in the mutagenic and carcinogenic potential of mustard gas This was followed by the work of Case and Lea, who examined the possible carcinogenic effects of H on exposed British soldiers. They cited total British gas casualties as 160,970, 80% of whom were estimated to have been H casualties. As of January 1,... 

In the review by Papirmeister et al. (1991), it was noted that sulfur mustard-induced cytotoxicity is dose dependent and that DNA appeared to be more sensitive to mustard-induced alkylation than are other cellular constituents. The low-dose effects of sulfur mustard are characterized by gen-otoxicity and inhibition of mitosis. The loss of cellular reproduction may be due to bifunctional alkylation that ultimately prevents normal DNA replication. It was hypothesized that monofunctional DNA damage might be responsible for low-dose mutagenic and possibly carcinogenic effects. 

Several of the Brassicaceae contain allyl isothiocyanate, which is a potent irritant and has mutagenic activity in bacteria and fetotoxic and carcinogenic effects in rats. However, as allyl isothiocyanate also occurs in ordinary mustard, it would not be realistic to ban aU botanical drugs that contain it, since they commonly provide no more than a normal daily dose of mustard (for example 5 mg of allyl isothiocyanate per 5 g of mustard). 

The chemical munitions cleanup problem is however complicated by the fact that, during World War II, Germany manufactured special preparations of mustard mixed with arsenic compounds of an exceedingly viscous and stable type, called "Zahlost". Both constituents had insidious properties including long-term carcinogenic effects. Moreover, they pose problems as to their disposal whether by wet chemical (hydrolysis) or thermal processes. 

Bone marrow toxicity is the major side effect of chlorambucil. Nausea is uncommon or mUd, and hair loss does not occur. Chlorambucil shares the immunosuppressive, teratogenic, and carcinogenic properties of the nitrogen mustards. 

PS is acutely toxic and has a variety of sensory effects in animals. It has not been evaluated thoroughly for mutagenicity or carcinogenicity. Like those exposed to mustard gas, the subjects exposed to PS were wearing gas masks, and small numbers of soldiers were exposed to small doses. PS is unlikely to have produced detectable long-term health effects in volunteers exposed at Edgewood. 

In general, the Committee found insufficient evidence to evaluate these chemicals, except mustard gas. Mustard gas 1b an experimental mutagen and human carcinogen at high doses. Data on the other irritants are insufficient to evaluate their mutagenicity, carcinogenicity, or other long-term effects. Tests of all these chemicals involved few exposures and low doses. 

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-... 

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. 

Animal carcinogen. Reasonably anticipated to be a human carcinogen and when used as a chemotherapeutic agent in combination with nitrogen mustard, a potent animal carcinogen, can result in acute nonlymphocytic leukemia.5 Adverse effects in 50-70% of... 

Considering all the above data, the U.S. EPA (1991) selected the unit risk of 8.5 x 10 per pg/m, derived from the Weibull time-to-tumor model, as the recommended upper bound estimate of the carcinogenic potency of sulfur mustard for a lifetime exposure to HD vapors. However, U.S. EPA (1991) stated that "depending on the unknown true shape of the dose-response curve at low doses, actual risks may be anywhere from this upper bound down to zero". The Weibull model was considered to be the most suitable because the exposures used were long-term, the effect of killing the test animals before a full lifetime was adjusted for, and the sample size was the largest obtainable from the McNamara et al. (1975) data. 

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. 

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