genic potency of nitrogen mustard appears to be similar to sulfur mustard. In addition, nitrogen mustard has been shown to be one of the most potent carcinogens amongst the alkylating agents tested in the strain A bioassay program of the National Cancer Institute.
Studies of these agents in humans have involved occupational, battlefield, and therapeutic exposures. Occupational exposure to sulfur mustard has been associated with respiratory tract cancer. The data from battlefield exposures, however, have been somewhat more equivocal: an excess of lung cancer was observed, but the excess was not statistically significant. Follow-up of cancer patients treated with nitrogen mustard derivatives has clearly indicated a causal association with skin cancer and leukemia, particularly the acute nonlymphocytic type. Although an excess of skin cancer or leukemia was not evident in the occupational or battlefield studies, the discrepancy may result from differences in amount of exposure; the leukemias or skin cancer may have occurred prior to the start of observation of the occupational and battlefield cohorts; or nonfatal cases of skin cancer may not have been detected in mortality studies. It is also possible that skin cancers did not occur in the studied populations, or that there was a difference in effects between sulfur and nitrogen mustards. Although nitrogen mustard-associated leukemia and skin cancer occur usually within a decade of therapeutic exposure, the occurrence of an excess of such cases among the WWII human subjects, Bari casualties, or workers would not be surprising.
The evidence indicates a causal relation between exposure to sufficient concentrations of sulfur mustard (and presumably nitrogen mustard and Lewisite) and chronic nonreversible respiratory effects in humans.
Follow-up of WWI battlefield casualties has demonstrated the association between exposure to sulfur mustard and development of chronic bronchitis, emphysema, and asthma. Chronic respiratory effects have also been shown in workers from WWII chemical weapons factories and casualties of the Iran-Iraq war. These results are well supported by studies in laboratory animals. Given the concentrations of mustard agents and Lewisite used in the WWII experiments, prior research predicts the development of chronic nonreversible lung diseases. Further, indirect evidence, based on a review of the relationships between acute and chronic effects caused by other substances, suggests that these long-term respiratory effects may occur in the absence of an acute respiratory response.
The evidence indicates a causal relation between exposure to sulfur mustard and recurrent corneal ulcerative disease (including corneal opacities), delayed recurrent keratitis, and chronic