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Suggested Citation:"References." Institute of Medicine. 2002. Veterans and Agent Orange: Herbicide/Dioxin Exposure and Acute Myelogenous Leukemia in the Children of Vietnam Veterans. Washington, DC: The National Academies Press. doi: 10.17226/10309.
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Suggested Citation:"References." Institute of Medicine. 2002. Veterans and Agent Orange: Herbicide/Dioxin Exposure and Acute Myelogenous Leukemia in the Children of Vietnam Veterans. Washington, DC: The National Academies Press. doi: 10.17226/10309.
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Page 24
Suggested Citation:"References." Institute of Medicine. 2002. Veterans and Agent Orange: Herbicide/Dioxin Exposure and Acute Myelogenous Leukemia in the Children of Vietnam Veterans. Washington, DC: The National Academies Press. doi: 10.17226/10309.
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Page 25

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HERBICIDE/DIOXIN EXPOSURE AND ACUTE MYELOGENOUS LEUKEMIA 23 2,4-D, 2,4,5-T, and dioxin (Lamb et al., 1980). The offspring of mice exposed to a mixture of 2,4-D and picloram showed some effects, but only at doses that also caused paternal toxicity (Blakley et al., 1989). The mechanism by which herbicide or TCDD exposures could lead to child- hood cancers in the offspring of persons exposed many years previously is unknown. One possible mechanism would involve germ cell mutations whereby damaged cells might later undergo spermatogenesis and result in fertilization, leading to the birth of a genetically susceptible child. However, assays do not indicate that the herbicides of interest or TCDD are genotoxic except at very high doses or concentrations. The link between Down syndrome and AML appears to imply some genetic origin of susceptibility for at least a portion of AML cases. Leukemias in younger children, the period during which childhood AML cases are more common, are believed to have a different etiology from those of older children because the genetic abnormalities underlying them are more likely to have been present at birth. The Committee is not aware of any information published since the release of Update 2000 that bears on the issue of the biologic plausibility of any associa- tion between paternal exposure to the herbicides used in Vietnam or dioxin and AML in offspring. Given the present lack of information, the committee believes that further research aimed at evaluating long-term effects of herbicide exposures on male reproductive organs and on understanding the effects on sex ratio and functional developmental toxicities would be useful. REFERENCES ACS (American Cancer Society). 2001. Cancer Reference Information. All About Leukemia— Children’s. http://www.cancer.org/eprise/main/docroot/CRI/CRI_2x?sitearea=CRI&dt=24 (accessed November 26, 2001). AIHW (Australian Institute of Health and Welfare). 1998. Morbidity of Vietnam Veterans: A Study of the Health of Australia’s Vietnam Veteran Community: Volume 1, Male Vietnam Veterans Survey and Community Comparisons Outcomes. Canberra: AIHW. AIHW. 1999. Morbidity of Vietnam Veterans: A Study of the Health of Australia’s Vietnam Veteran Community: Volume 3, Validation Study. Canberra: AIHW. AIHW. 2000. Morbidity of Vietnam veterans. Adrenal gland cancer, leukaemia and non-Hodgkin’s lymphoma: Supplementary report no. 2. (AIHW cat. no. PHE 28). Canberra: AIHW. AIHW. 2001. Morbidity of Vietnam veterans. Adrenal gland cancer, leukaemia and non-Hodgkin’s lymphoma: Supplementary report no. 2. Revised edition (AIHW cat. no. PHE 34). Canberra: AIHW. Bertazzi PA, Zocchetti C, Pesatori AC, Guercilena S, Consonni D, Tironi A, Landi MT. 1992. Mortality of a young population after accidental exposure to 2,3,7,8-tetrachlorodibenzodioxin. International Journal of Epidemiology 21(1):118–123. Blakley PM, Kim ES, Firneisz GD. 1989. Effects of paternal subacute exposure to Tordon 202c on fetal growth and development in CD-1 mice. Teratology 39(3):237–241.

24 VETERANS AND AGENT ORANGE Buckley JD, Robison LL, Swotinsky R, Garabrant DH, LeBeau M, Manchester P, Nesbit ME, Odom L, Peters JM, Woods WG, Hammond GD. 1989. Occupational exposures of parents of children with acute nonlymphocytic leukemia: A report from the Childrens’ Cancer Study Group. Cancer Research 49:4030–4037. CDC. 1989. Health Status of Vietnam Veterans. Vietnam Experience Study, Vol. V, Reproductive Outcomes and Child Health. Atlanta: U.S. Department of Health and Human Services. CDVA (Commonwealth Department of Veterans’ Affairs). 1998. Morbidity of Vietnam Veterans: A Study of the Health of Australia’s Vietnam Veteran Community. Vol. 1: Male Vietnam Veterans Survey and Community Comparison Outcomes. Canberra: Department of Veterans’ Affairs. Erickson JD, Mulinare J, McClain PW, Fitch TG, James LM, McClearn AB, Adams MJ. 1984. Vietnam veterans’ risks for fathering babies with birth defects. Journal of the American Medi- cal Association 252(7):903–912. Field B, Kerr C. 1988. Reproductive behaviour and consistent patterns of abnormality in offspring of Vietnam veterans. Journal of Medical Genetics 25:819–826. Heacock H, Hertzman C, Demers PA, Gallagher R, Hogg RS, Teschke K, Hershler R, Bajdik CD, Dimich-Ward H, Marion SA, Ostry A, Kelly S. 2000. Childhood cancer in the offspring of male sawmill workers occupationally exposed to chlorophenate fungicides. Environmental Health Perspectives 108:499–503. Hill AB. 1971. Principles of Medical Statistics, 9th Ed. New York: Oxford University Press. Hoar SK, Morrison AS, Cole P, Silverman DT. 1980. An occupation and exposure linkage system for the study of occupational carcinogenesis. Journal of Occupational Medicine 22:722–726. IOM (Institute of Medicine). 1994. Veterans and Agent Orange: Health Effects of Herbicides Used in Vietnam. Washington, DC: National Academy Press. IOM. 1996. Veterans and Agent Orange: Update 1996. Washington, DC: National Academy Press. IOM. 1997. Characterizing Exposure of Veterans to Agent Orange and Other Herbicides Used in Vietnam: Scientific Considerations Regarding a Request for Proposals for Research. Washing- ton, DC: National Academy Press. IOM. 1999. Veterans and Agent Orange: Update 1998. Washington, DC: National Academy Press. IOM. 2000. Veterans and Agent Orange: Herbicide/Dioxin Exposure and Type 2 Diabetes. Washing- ton, DC: National Academy Press. IOM. 2001. Veterans and Agent Orange: Update 2000. Washington, DC: National Academy Press. Kristensen P, Andersen A, Irgens LM, Bye AS, Sundheim L. 1996. Cancer in offspring of parents engaged in agricultural activities in Norway: Incidence and risk factors in the farm environ- ment. International Journal of Cancer 65(1):39–50. Lamb JC, Moore JA, Marks TA. 1980. Evaluation of 2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5- trichlorophenoxyacetic acid (2,4,5-T), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity in C57BL/6 mice. Reproduction and Fertility in Treated Male Mice and Evaluation of Con- genital Malformations in Their Offspring. National Toxicology Program. Langmuir PB, Aplenc R, Lange BJ. 2001. Acute myeloid leukaemia in children. Best Practice & Research Clinical Haematology 14(1):77–93. Meinert R, Schüz J, Kaletsch U, Kaatsch P, Michaelis J. 2000. Leukemia and non-Hodgkin’s lym- phoma in childhood and exposure to pesticides: Results of a register-based case-control study in Germany. American Journal of Epidemiology 151(7):639–646. NCI (National Cancer Institute). 2002. Surveillance, Epidemiology, and End Results (SEER) Program, Cancer Query System 2.0. http://www.seer.cancer.gov/ScientificSystems/Canques (accessed February 13). Pesatori AC, Consonni D, Tironi A, Zocchetti C, Fini A, Bertazzi PA. 1993. Cancer in a young population in a dioxin-contaminated area. International Journal of Epidemiology 22(6):1010– 1013.

HERBICIDE/DIOXIN EXPOSURE AND ACUTE MYELOGENOUS LEUKEMIA 25 Robison LL, Buckley JD, Daigle AE, Wells R, Benjamin D, Arthur DC, Hammond GD. 1989. Maternal drug use and risk of childhood nonlymphoblastic leukemia among offspring. An epidemiologic investigation implicating marijuana (a report from the Childrens Cancer Study Group). Cancer. 63(10):1904–1911. Ross JA, Potter JD, Reaman GH, Pendergrass TW, Robison LL. 1996. Maternal exposure to poten- tial inhibitors of DNA topoisomerase II and infant leukemia (United States): a report from the Children’s Cancer Group. Cancer Causes Control 7(6):581–590. Severson RK, Buckley JD, Woods WG, Benjamin D, Robison LL. 1993. Cigarette smoking and alcohol consumption by parents of children with acute myeloid leukemia: an analysis within morphological subgroups—a report from the Childrens Cancer Group. Cancer Epidemiology, Biomarkers and Prevention 2(5):433–439. Song F, Eastwood AJ, Gilbody S, Duley L, Sutton AJ. 2000. Publication and related biases. Health Technology Assessment 4(10):1–115. Wen WQ, Shu XO, Steinbuch M, Severson RK, Reaman GH, Buckley JD, Robison LL. 2000. Paternal military service and risk for childhood leukemia in offspring. American Journal of Epidemiology 151(3):231–240.

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In 2001, in response to a request by the U.S. Department of Veterans Affairs (DVA), the Institute of Medicine (IOM) called together a committee to conduct a review of the scientific evidence regarding the association between exposure to dioxin and other chemical compounds in herbicides used in Vietnam and acute myelogenous leukemia in the offspring of Vietnam veterans. Based on the scientific evidence reviewed in this report, the committee finds there is inadequate or insufficient evidence to determine if an association exists between exposure to the herbicides used in Vietnam or their contaminants and acute myelogenous leukemia (AML) in the children of Vietnam veterans. This is a change in classification from the recent Veterans and Agent Orange: Update 2000 report, which found limited/suggestive evidence for such an association.

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