Veterans and Agent Orange Update 2014 (2016) / Chapter Skim
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In 1991, because of continuing uncertainty about long-term health effects of the sprayed herbicides in Vietnam veterans, Congress passed Public Law (PL) 1 Despite loose usage of "Agent Orange" by many people, in numerous publications, and even in the title of this series, this committee uses "herbicides" to refer to the full range of herbicide exposures experienced in Vietnam, while "Agent Orange" is reserved for a specific one of the mixtures sprayed in Vietnam.
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hether a statistical association with herbicide exposure exists, taking w into account the strength of the scientific evidence and the appropriate ness of the statistical and epidemiological methods used to detect the association; B) he increased risk of disease among those exposed to herbicides during t service in the Republic of Vietnam during the Vietnam era; and C)
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COMMITTEE'S APPROACH TO ITS CHARGE Following the pattern established by prior VAO committees, the present committee concentrated its review on epidemiologic studies to fulfill its charge of assessing whether specific human health effects are associated with exposure to at least one of the herbicides sprayed in Vietnam or to TCDD. The committee also considered controlled laboratory investigations that provided information on whether a scientifically relevant association between the chemicals of interest and a given effect is biologically plausible.
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For these conditions, unless the condition is logically subsumed under a broader disease category that has been evaluated, the committee remains neutral, abiding by the maxim that "absence of evidence is not evidence of absence." In accordance with Congress's mandated presumption of herbicide exposure of all Vietnam veterans, VAO committees have treated Vietnam-veteran status as a proxy for some herbicide exposure when no more specific exposure information is available. To anticipate health conditions associated with aging that might differentially affect Vietnam veterans and to obtain additional information potentially relevant to the evaluation of health effects in Vietnam veterans, the committees have reviewed studies of other groups potentially exposed to the constituents present in the herbicide mixtures used in Vietnam (2,4-D, 2,4,5-T, TCDD, cacodylic acid, and picloram)
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Although not required, data supporting biologic plausibility can strengthen confidence that an association is not spurious and are presented in each of the sections. In this regard, it is important to note that while the biologic plausibility for a particular effect has been considered sufficient evidence of asso iation by several international review boards, the Agent Orange Act requires c
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model developed with the encouragement of earlier VAO committees. Estimates of potential herbicide exposure were calculated for each veteran on the basis of military records of the movements of the individual service units merged with a model of location and time of US herbicide spray missions reconstructed from the records of Operation Ranch Hand.
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Case-Control Studies Additional articles evaluating exposures to pesticides and phenoxy herbicides in particular came from the Cross-Canada Study of Pesticides and Health, which focuses on lymphoid neoplasms, and from the National Birth Defects Prevention Study. Four new separate case-control studies also addressed lymphohematopoietic conditions in relation to the chemicals of interest, while a final case-control study was concerned with male infertility.
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Inadequate or Insufficient Evidence to Determine an Association The available epidemiologic studies are of insufficient quality, consistency, or statistical power to permit a conclusion regarding the presence or absence of an association. For example, studies fail to control for confounding, have inadequate exposure assessment, or fail to address latency.
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Neonatal or infant death and stillbirth in offspring of exposed people Low birth weight in offspring of exposed people Birth defects in offspring of exposed people (category change from Limited or Suggestive in Update 2012 for spina bifida) Childhood cancer (including acute myeloid leukemia)
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In addition, the possibility of a very small increase in risk at the exposure studied can never be excluded. There is limited or suggestive evidence of no association between exposure to the herbicide component of interest and the following health outcome: Spontaneous abortion after paternal exposure to TCDD aHerbicides indicates the following chemicals of interest: 2,4-dichlorophenoxyacetic acid (2,4-D)
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The original VAO committee concluded that there was little and inconsistent evidence for an association between paternal exposure and birth defects in general. At the time of the first VAO update, the only additional information the committee had to consider was a publication from the Air Force Health Study (AFHS)
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Consequently, spina bifida in the offspring of Vietnam veterans has been moved to the category of "inadequate or insufficient" evidence of an association with herbicide exposure along with all other types of birth defects. (This is only the second time that a VAO committee has demoted a health outcome to a weaker category of association than it had been in before; the first instance was the move of porphyria cutanea tarda from the "sufficient" category to the "limited or suggestive" category by the committee for Update 1998.)
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Exposures were not intentionally monitored during the Vietnam War, but there have been concerted efforts over the nearly 50 years since the end of the conflict to reconstruct the herbicide exposures experienced by US veterans during their service in Vietnam. Nonetheless, we remain completely out of range of the ideal of having reliable estimates of the intensity and duration of every soldier's exposure to each of the five chemicals of interest, and with the passage of time, it has become increasingly unlikely that even semiquantitative group estimates will ever be obtained.
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More recent studies of health consequences in the maturing veterans themselves, however, have generated more informative findings than were available to earlier VAO committees. The committee believes that there is sufficient evidence to reach general or qualitative conclusions about associations between herbicide exposure and health outcomes, but the lack of adequate exposure data on Vietnam veterans themselves makes it difficult to estimate the degree of increased risk of disease in Vietnam veterans as a group or individually.
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For outcomes categorized as having "sufficient" or "limited or suggestive" evidence of an association with herbicide exposure, the lack of exposure information on Vietnam veterans prevents the calculation of precise risk estimates. The present committee agrees with the assessment of previous committees that it is not now possible to derive quantitative estimates of any increased risks of various adverse health effects that Vietnam veterans may have experienced in association with exposure to the herbicides sprayed in Vietnam.
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EPIDEMIOLOGIC STUDIES Air Force Health Study (AFHS) Comprehensive longitudinal analysis of the AFHS data collected in the six intensive medical-cycle examinations (particularly concerning medical interventions, cancer incidence, mortality, birth defects in veterans' offspring)
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assess exposure to include the chemicals of interest to VAO committees. Consideration of the experience of VA's own patients might also provide insight into the role of exposures unique to military service in common conditions that are recognized to have a multitude of contributing etiologic factors.
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Because the biological plausibility of paternal transmission of adverse effects remains to be established, effort should be invested in the development of epidemiologic protocols to address the logistical challenge of tracing adverse effects in the adult children and grandchildren of Vietnam veterans that are sufficiently robust to detect any actual effect associated specifically with exposures experienced by male veterans. It is the committee's conviction that work needs to be undertaken promptly to resolve questions regarding several health outcomes, such as COPD, tonsil cancer, melanoma, Alzheimer disease, and paternally transmitted effects in offspring.
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