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TABLE I-1 Comparative Carcinogenicity of Selected Agents in Strain A Mice

Compound

Response Dosea

Relative Potencyb

Uracil mustard

0.96

10,420

Nitrogen mustard

3.0

3,300

Melphalan

3.8

2,630

Aziridyl benzoquinone

12

830

Chloroquine mustard

18

560

Chlorambucil

60

170

Cyclophosphamide

360

28

a The total dose required to produce 1.0 tumor per mouse at 39 weeks.

b 10,000 divided by the response dose.

SOURCE: Shimkin et al., 1966.

into a cancer potency that is only one-fifth that of aflatoxin B1 for liver tumors (aflatoxin B1 TD50 = 4.19 µg in male rats). Because that experimental cancer potencies can differ by as much as 10 million-fold, these data suggest similar potencies for HN2 and aflatoxin B1.

In a study comparing the effects of HN2 and other radiomimetic chemicals with the effects of X-radiation, Conklin and colleagues (1965) found the incidence of thymic lymphoma from four injections of 2.4 mg/kg each to be less than that of four doses of 300 rads each of X-rays (21 percent lymphoma incidence for HN2, 33 percent for X-radiation, 10 percent for controls). Thus, the midlethal doses of HN2 were similar to midlethal doses of X-radiation.

CANCER RISKS FROM SIMILAR COMPOUNDS

A  variety of mustard compounds are used in chemotherapy or treatment of other diseases. Many of these have also demonstrated a potential to produce malignancy during or following treatment. Sulfur mustard, HN2, and these other mustards are alkylating agents. It is believed that they act by producing interstrand and intrastrand DNA-DNA cross-links; this action may be related to carcinogenic effects (Colvin and Chabner, 1990). While the pharmacokinetics of the alkylation process differs for the different chemicals, the similarity of ultimate action suggests that data on the carcinogenic potential of these other mustard compounds may be relevant to the risks of developing cancer from exposure to sulfur mustard.

A malignancy commonly arising from treatment by alkylating agents is acute nonlymphocytic leukemia (ANL). Of the various medicinal mustard compounds, good data on human exposure-based risk of developing ANL are available for chlorambucil, cyclophosphamide, and



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