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Veterans at Risk: The Health Effects of Mustard Gas and Lewisite
importance of this experiment is not that of a potency estimate, but that of clear evidence of lifetime risk of pulmonary tumors from a 15-minute inhalation exposure.
The inhalation chamber exposures of McNamara and colleagues (1975) present the best available experimental data on sulfur mustard carcinogenicity (Tables 6-5 and 6-6). Of the rats exposed to 0.1 mg/m3 for 6.5 hours 5 days per week for 52 weeks, 10 of 23 developed agent-related tumors in a ''carcinogenicity study" and 9 of 39 in a "toxicity study." Of the 19 tumors, 17 were either squamous cell or basal cell carcinoma of the skin. No carcinomas were present in 52 control mice observed for similar periods. In the atmospheric exposure experiments of McNamara and colleagues, it should be noted that the only excess malignancies in exposed groups were skin tumors. With the exception of exposed strain A/J mice (which developed pulmonary tumors, but not in excess), no pulmonary tumors in any exposed group were reported in these inhalation experiments. Further, at similar inhalation exposures, but inadequate follow-up time, McNamara and colleagues observed no increase in agent-related skin or other malignancies in experiments with dogs, guinea pigs, rabbits, and A/J mice. The skin malignancies, however, are noteworthy. First, their cumulative incidence in the high-exposure group approached 50 percent. Second, the absence of other tumors suggests that the skin malignancies were the result of external, rather than systemic, exposure. This suggests that similar or even lower cumulative air exposures may be of concern for human skin carcinogenicity, particularly in combination with high exposure to sunlight.
Because of a similar structure and toxicity, malignancies caused by nitrogen mustard (HN2) are also of interest. The intravenous and subcutaneous experiments using HN2 by Heston (1950, 1953a) have been mentioned above.
Another study by Shimkin and colleagues (1966) reviewed early National Cancer Institute bioassay data for 29 alkylating chemicals tested in strain A mice. Of the 29 compounds, the potency of HN2-HCl in producing pulmonary nodules was exceeded only by uracil mustard. The data for the five most potent compounds and that for chlorambucil and cyclophosphamide are shown in Table I-1.
Gold and colleagues (1984) reported a TD50 for all malignancies of 22.8 µg (0.0456 mg/kg) for HN2, based on laboratory rat data from Schmähl and Osswald (1970). TD50 is the cumulative exposure that is expected to produce an excess cancer mortality of 50 percent in a two-year followup; a low TD50 indicates a high potency. The TD50 for HN2 translates