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lan and chlorambucil, and the alkylating carcinogenic compound, bis(chloromethyl) ether. Comparisons of laboratory rodent data indicated that sulfur mustard and nitrogen mustard had tumorigenic potencies comparable with melphalan and bis(chloromethyl) ether; the tumorigenic potencies of sulfur and nitrogen mustard were possibly greater than that of chlorambucil.

RELEVANCE OF EXPERIMENTAL RESULTS TO HUMAN RISKS

The above observations and comparisons indicate that sulfur mustard is an animal carcinogen and, to the extent that its action is similar to HN2, a potent one. Both excess pulmonary tumors and skin malignancies were demonstrated to occur from sulfur mustard exposure in experimental studies. Such data are in agreement with

  •  excess lung cancer observed in groups of individuals occupationally exposed during sulfur mustard production; and

  •  skin cancer observed in patients undergoing topical treatment with therapeutic concentrations of nitrogen mustard.

Data from studies of effects of exposure to therapeutic nitrogen mustards are suggestive of risks of additional malignancies. Mustard compounds used as chemotherapeutic agents have demonstrated a high potential to generate acute nonlymphocytic leukemia. The similarity between the alkylating action of these compounds and sulfur mustard suggests that sulfur mustard exposure might also result in such malignancies. This is also suggested by the finding of an increased incidence of thymic lymphoma in female strain RF mice injected with HN2.

In summary, experimental studies establish that exposure to sulfur mustard produces a substantial risk of lung tumors in laboratory animals and also produces a risk of skin cancer from air exposure. For each pathological site, the cancer potency of sulfur mustard is high. Experimental data from exposures to HN2 suggest that sulfur mustard exposure may lead to an increased risk of developing thymic lymphoma, and perhaps acute nonlymphocytic leukemia, based on findings in humans treated with therapeutic alkylating agents.

HUMAN EXPOSURES

Mustard agents were positively associated with human respiratory tract cancer incidence by the International Agency for Research on Cancer (IARC) in 1975. By 1981, IARC had categorized "mustard gas" as a "Class 1" human carcinogen (Saracci, 1981). Exposure and dose-response data are not available that would allow precise risk estimates to



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