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found to be a carcinogen. It produced pulmonary tumors from both intravenous and intraperitoneal injections in strain A mice. Subcutaneous exposures produced injection site tumors and pulmonary tumors in selected strains of mice. Its carcinogenic potency appeared to be similar to sulfur mustard, and it was one of the most potent carcinogens amongst the alkylating agents tested in the strain A bioassay program.

Evidence indicates that occupational exposure to sulfur mustard is associated with respiratory tract cancer. The battlefield experience is somewhat more equivocal, although the lung cancer excess is suggestive of an association.

Evidence from therapeutic use of nitrogen mustard clearly indicates a causal association with skin cancer (see Chapter 9) and leukemia. An excess of skin cancer or leukemia was not evident in the occupational or battlefield studies.

The weight of the evidence—cellular, epidemiological, and toxicologic—indicates a causal association between sulfur mustard exposure and the occurrence of excess respiratory cancer, and skin cancer, and possibly leukemia. Inadequate exposure information limits accurate estimation of the cancer excesses that may be expected. The evidence is insufficient to indicate a causal relationship for Lewisite carcinogenesis.

Based on the foregoing, the committee concludes that human subjects of the WWII chamber tests are probably at increased risk of respiratory tract and skin cancer. This conclusion is based upon estimates of exposure to sulfur mustard that occurred among the subjects of the chamber tests (see Chapter 3), which approximated the battlefield exposure of surviving WWI soldiers. Studies of WWI gassing victims demonstrate a suggestive excess of cancer of the respiratory tract. Limitations on information on exposure of study subjects and WWI gassing victims limit the precision of this risk projection.

REFERENCES

Abell CW, Falk HL, Shimkin MB. 1965. Uracil mustard: a potent inducer of lung tumors in mice. Science 147:1443-1445.

Ashby J, Tinwell H, Callander RD, Clare N. 1991. Genetic activity of the human carcinogen sulfur mustard toward Salmonella and the mouse bone marrow. Mutation Research 257:307-312.

Auerbach C. 1943. Chemically induced mutations as rearrangements. Drosophila Information Service 17:48-50.

Auerbach C. 1951. The effect of oxygen concentration on the mutagenic action of mustard gas. Kurze Mitteilungen 15:341-342.

Auerbach C, Moser H. 1950. Production of mutations by monochloro-mustards. Nature 166:1019-1020.

Auerbach C, Robson JM. 1946. Chemical production of mutations. Nature 157:302.

Auerbach C, Robson JM. 1947. Production of mutations by chemical substances. Proceedings of the Royal Society of Edinburgh. Section B: Biology 62:271-283.



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