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Veterans at Risk: The Health Effects of Mustard Gas and Lewisite (1993)
Institute of Medicine (IOM)

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. "6 Relationship of Mustard Agent and Lewisite Exposure to Carcinogenesis." Veterans at Risk: The Health Effects of Mustard Gas and Lewisite. Washington, DC: The National Academies Press, 1993.

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Veterans at Risk: The Health Effects of Mustard Gas and Lewisite

TABLE 6-1 Pulmonary Tumors in Strain A  Mice Injected Intravenously with Nitrogen Mustard and Sulfur Mustard

Experiment

Follow-up Duration

No. of Mice

% with Nodules

Mean No. of Nodules

Nitrogen mustard

Experiment I: two to four intravenous injections of 1 mg/kg HN2 (14 received 4 injections; 22 received 3; and one, 2) at 2-day intervals

13-16 wks

29

100

3.48

Control

13-16 wks

30

13

0.17

Experiment II: Four intravenous injections of 1 mg/kg HN2 at 2-day intervals

10 mos

20

100

9.60

Control

10 mos

32

63

0.81

Experiment III: One intravenous injection of 4 mg/kg HN2

10 mos

9

100

7.56

Control

10 mos

31

58

0.94

Sulfur mustard

Experiment IV: Four intravenous injections of 0.65 mg/kg at 2-day intervals

16 wks

15

93

2.60

Control

16 wks

28

61

0.93

Experiment V: Four intravenous injections of 0.65 mg/kg at 2-day intervals

16 wks

47

69

1.09

Control

16 wks

46

13

0.13

 

SOURCE: Heston, 1949, 1950.

high early mortality: 9 males and 4 females of 30 animals injected died shortly after completion of the injections. The results for the animals surviving 16 weeks showed somewhat fewer mice with lung nodules and a lower mean number of nodules compared to Experiment I with HN2. Further, an unusually high number of controls developed adenomas for which no cause could be identified. When Experiment IV was repeated as Experiment V, by using a lower concentration of sulfur mustard, fewer mice developed lung nodules (68 vs. 93 percent) and the mean number of lung nodules was substantially less (1.09 vs. 2.60). Obviously, there is uncertainty about the actual dose to the animals in the sulfur mustard experiments, particularly in Experiment IV, where the administered dose may have exceeded 1 mg/kg body weight.

A later study by Heston and colleagues (1953) compared the separate and combined effects of intravenous HN2 and X-irradiation (Table 6-2). With only two injections of 1 mg/kg HN2, some animals were tumor free

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90
Front Matter (R1-R20)
Executive Summary (1-8)
1 Introduction (9-13)
2 Methods of Literature Collection and Survey (14-20)
3 History and Analysis of Mustard Agent and Lewisite Research Programs in the United States (21-60)
4 Findings from the Public Hearing Process (61-70)
5 Chemistry of Sulfur Mustard and Lewisite (71-80)
6 Relationship of Mustard Agent and Lewisite Exposure to Carcinogenesis (81-111)
7 Nonmalignant Respiratory Effects of Mustard Agents and Lewisite (112-130)
8 Ocular Effects of Mustard Agents and Lewisite (131-147)
9 Dermatological Effects of Mustard Agents and Lewisite (148-178)
10 Other Physiological Effects of Mustard Agents and Lewisite (179-198)
11 Relationship of Mustard Agent and Lewisite Exposure to Psychological Dysfunction (199-213)
12 Summary of Findings and Recommendations (214-226)
Bibliography (227-330)
A. Scientific and Background Presentations Made to the Committee (331-334)
B. Excerpt from The Residual Effects of Warfare Gases (335-337)
C. Involvement of the National Academy of Sciences Complex in World War II Research Programs: A Summary (338-339)
D. Excerpts from Chamber Tests with Human Subjects I, II, and IX. Naval Research Laboratory Reports Nos. P-2208 and P-2579 (340-369)
E. Interim Report and Addendum: Feasibility of Developing a Cohort of Veterans Exposed to Mustard Gas During WWII Testing Programs (370-377)
F. Summary of the Department of the Army Report: Use of Volunteers in Chemical Agent Research (378-381)
G. Public Hearing Announcement (382-385)
H. Letter from Dr. Jay Katz to Dr. David P. Rall (386-389)
I. Risk Assessment Considerations for Sulfur Mustard (390-398)
J. Examination of the Effects of Certain Acute Environmental Exposures on Future Respiratory Health Consequences (399-416)
List of Acronyms and Abbreviations (417-420)
Index (421-428)