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10 Other Physiological Effects of Mustard Agents and Lewisite
Pages 179-198

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From page 179...
... This chapter reviews the animal experimental data and human epidemiological studies that have focused on the following systems: 0 immune system, including blood lymphocytes, lymphatic tissues, and bone marrow; 0 gastrointestinal system; 0 blood system; o nervous system, including autonomic and higher-order functions; and · reproductive risks. EFFECTS ON THE IMMUNE SYSTEM Anatomy and Physiology The human body has the ability to resist many types of organisms or toxic agents to which it may be exposed.
From page 180...
... Clonal expansion increases the number of these specifically reactive T and B cells, so that subsequent exposure to the same antigen leads to a rapid specific immune response. As an immune response occurs, a decrease of the T cells is likely, and negative feedback into earlier phases prevents excessive reaction.
From page 181...
... Chemicals that suppress bone marrow function can affect reserves of stem cells that are needed for cell replacement. Blood line cells are derived from stem cells, which can develop into many cell types (pluripotent)
From page 182...
... Quantitative histologic investigation of the effects of intravenously injected sulfur and nitrogen mustard on albino rats suggested a decreased immunoresponsiveness, expressed as leukopenia, lymphopenia, and neutropenia (the disappearance of the respective blood cells) , as well as hypoplasia and hyperemia of bone marrow.
From page 183...
... Stewart (1918) studied 10 fatal cases of mustard poisoning and observed shilling depression of bone marrow production of white blood cells.
From page 184...
... In another study, the femoral bone marrow in 55 of 75 autopsies of mustard gas-exposed patients was examined (Krumbhaar and Krumbhaar, 1919~. The results: 14 marrows were classified as showing almost no regenerative potential; 8 showed only slight reaction; and only 13 showed moderate reaction.
From page 185...
... As a result, these agents are particularly toxic to rapidly proliferating cells including neoplastic, lymphoid, and bone marrow cells. Because of these immunosuppressive effects, sulfur and nitrogen mustards have particular clinical importance.
From page 186...
... Clinical observations in humans provide the most direct evidence of the immunologic effects of mustard agents. In this review, greater significance was accorded to observations in humans that provide clear evidence that mustard agent exposure is associated with bone marrow toxicity expressed as leukopenia, pancytopenia, or aplastic or hypoplastic bone marrow.
From page 187...
... Hematological Effects In animals exposed to very high doses (i.e., LD50) of mustard agents, aplastic changes occur in the bone marrow.
From page 188...
... To what extent these can be attributed to mustard agents rather than other chemical warfare agents is unclear, but other exposures at this facility included known nerve agents. Renal and cardiac effects do not appear to occur after human exposures to mustard gas other than as secondary effects in severely affected individuals.
From page 189...
... They also suggest that sulfur mustards could be a reproductive toxin. Animal Studies Sulfur mustards induce dominant lethal mutations in Drosophila.
From page 190...
... used electrophoresis to study blood protein variants in 456 children of 325 workers exposed occupationally to sulfur mustard and Lewisite at the Okunojima poison gas factory; children were divided into three exposure groups based upon parental job category within the plant. The blood protein analysis revealed 6 types of protein variants in 11 children, and 11 variant erythrocyte proteins in 25 children.
From page 191...
... It appears to contain, however, the only other human data that attempt to address the reproductive toxicity of sulfur mustards. It should also be noted that other animal studies have shown that the structurally similar nitrogen mustards are potent teratogens (Danforth and Center, 1954; Haskin, 1948; Murphy et al., 1958; Sanyal et al., 1981~.
From page 192...
... There has been insufficient follow-up of the occupational or battlefield cohorts to determine the nature of any reproductive toxicity or teratogenic effects attributable to these exposures. Evidence suggests a causal relationship between sulfur mustard exposure and reproductive toxicity in laboratory animals, but the database is far too small and uncertain to allow a clear understanding of human reproductive risk from exposure to sulfur mustards.
From page 193...
... studied intravenous administration of sodium dimethylarsonate in pregnant CD-1 mice. On day 9 and 10 they observed increased fetal resorption and mortality rates, with increased incidence of skeletal malformations and exencephaly.
From page 194...
... The committee also received information from Colonel Richard Solana of the U.S. Anny Research Institute of Chemical Defense concerning unpublished data on the reproductive toxicity of Lewisite (Appendix A)
From page 195...
... It then would be more clear that the differences in reproductive toxicity between some arsenicals and Lewisite are not related to the bioconversion of Lewisite or to select spec~es-specific action of these compounds. The studies of the reproductive toxicity of Lewisite in laboratory animals are negative and are therefore insufficient to indicate a causal relationship between exposure and adverse reproductive outcomes.
From page 196...
... 1987. Teratology studies of Lewisite and sulfur mustard agents: effects of Lewisite in rats and rabbits.
From page 197...
... l919b. Bone marrow changes in mustard gas poisoning.
From page 198...
... 1985. Study of genetic effects of sulphur mustard gas on former workers of Okunojima poison gas factory and their offspring.


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