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I. Risk Assessment Considerations for Sulfur Mustard
Pages 390-398

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From page 390...
... Experimental animal data can be used to make estimates of carcinogenic potency in humans by using cancer risk models and standard interspecies extrapolation procedures. Unfortunately, quantitative human cancer risk estimates for sulfur mustard are impractical because the experimental data from animal studies have three large uncertainties: · only a few experiments were conducted; · many were in a mouse strain that exhibited a high genetic susceptibility to spontaneous pulmonary tumors; · routes of administration tested and duration of follow-up observations are not comparable to the human exposures of concern.
From page 391...
... Table ~1 does indicate that sulfur and nitrogen mustards have a similar potential to produce pulmonary tumors in this strain. This conclusion follows from the finding that the number of nodules produced from comparable injections of sulfur or nitrogen mustard is similar at 16 weeks of follow-up.
From page 392...
... Another study by Shimlcin and colleagues (1966) reviewed early National Cancer Institute bioassay data for 29 alkylating chemicals tested in strain A mice.
From page 393...
... 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)
From page 394...
... of the reciprocal of the TD50's for various antineoplastic drugs plotted against the relative human leukemogenic potency. No data exist that would allow a direct estimate to be made of the human leukemia potency index for HN2-HCl, but its TD50 in male rats (0.23 mglkg per day)
From page 395...
... This approach compares exposures that produce documented toxic effects from an agent of interest to exposures of a reference chemical producing a similar effect Jones et al., 1985, 1988~. The results of these relative potency analyses are usually similar to those of the more traditional CAG (Carcinogen Assessment Group)
From page 396...
... 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.
From page 397...
... Cancer Research 52:2464 2467. Glass LR, Easterly CE, Jones TD, Walsh PI.
From page 398...
... Journal of the National Cancer Institute 36:915-935. Watson AP, Jones TD, Griffin GD.


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