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Veterans at Risk: The Health Effects of Mustard Gas and Lewisite
orders of magnitude between highly potent carcinogens, such as aflatoxin B1, and carcinogens of very much lower potency, such as saccharin.
Two sets of experiments provide information on the carcinogenicity of sulfur mustard (see Chapter 6). One is the series of injection studies of Heston and colleagues (1949, 1950, 1953a) using strains A and C3H mice. These studies are difficult to interpret because of the extreme sensitivity of strain A mice for development of pulmonary tumors and the use of only subcutaneous injections in studies using the strain C3H mice. The second experiments are the chamber exposure studies of McNamara and colleagues (1975) in which Sprague-Dawley-Wistar rats were exposed to air concentrations of 0.001 and 0.1 mg/m3 for various periods of time up to 52 weeks. These latter experiments are more useful because of the long durations of exposure and long subsequent follow-up periods.
A comparison of the results of the intravenous injection studies of Heston (1950) indicates that both sulfur mustard and nitrogen mustard (HN2) readily produce pulmonary tumors in strain A mice. However, because of the high genetic susceptibility for development of pulmonary tumors in this strain of mice, it is inappropriate to make quantitative estimates of risk from these data alone. Table 6-1 does indicate that sulfur and nitrogen mustards have a similar potential to produce pulmonary tumors in this strain. This conclusion follows from the finding that the number of nodules produced from comparable injections of sulfur or nitrogen mustard is similar at 16 weeks of follow-up. This similarity and the similarity of DNA alkylation action make HN2 data relevant to evaluating the carcinogenic potency of sulfur mustard. However, caution must be exercised, because the pharmacokinetics of the two compounds differ. Sulfur mustard is more rapidly metabolized and may not act at distant sites as readily as HN2. This is seen in the strain C3H and C3Hf subcutaneous injection studies of Heston (1953a) where injection site malignancies were similar for both sulfur mustard and HN2, yet only HN2 produced an excess of pulmonary tumors (see Table 6-3).
The single inhalation study by Heston (1953b) is also inappropriate to use for estimating either animal or human cancer potency: first, because strain A mice were used; and second, because of the extremely large uncertainty of the exposure concentration tested. In this study, sulfur mustard evaporated from a soaked filter paper and was distributed by a fan through an 8-liter desiccator. The actual concentration of sulfur mustard during a 15-minute inhalation exposure is unknown. The