Veterans and Agent Orange Update 11 (2018) (2018) / Chapter Skim
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, the most toxic form of dioxin, was an unintended contaminant generated during the production of 2,4,5-T and so was present in Agent Orange as well as some of the other formulations sprayed in Vietnam. Concerns from returning Vietnam veterans about their own health and that of their children combined with emerging toxicologic evidence of the adverse effects of phenoxy herbicides and TCDD exposure from animal studies and some positive findings from epidemiologic studies led Congress to pass Public Law (PL)
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The current update presents this committee's review of peer-reviewed scientific reports concerning associations between various health outcomes and exposure to TCDD and other chemicals in the herbicides used in Vietnam that were published between September 30, 2014, and December 31, 2017, and the committee's integration of this information with the previously established evidence database. CHARGE TO THE COMMITTEE The committee was asked to "determine (to the extent that available scientific data permit meaningful determinations)
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COMMITTEE'S APPROACH TO ITS CHARGE Following the pattern established by previous VAO committees, the present committee concentrated its review on epidemiologic studies so as 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 examined controlled laboratory investigations that provided information on whether a scientifically relevant association between the COIs and a given effect is biologically plausible.
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Tables on individual health outcomes summarizing the salient results of epidemiologic studies that have been evaluated over the entire series of VAO reports have been compiled and are available in digital form from www.nap.edu/ catalog/25137. The results for a particular endpoint are grouped by study population to emphasize and clarify the relationship among successive publications based on the repeated study of particular exposed populations.
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A new study of hypertension in Army Chemical Corps personnel, who managed ground spraying operations, was also reviewed. Researchers using data from VA's Agent Orange Registry, a database containing health information on Vietnam veterans who voluntarily undergo examinations in a VA medical center, produced papers on various health outcomes that relied on surrogates of herbicide exposure such as self-reports.
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and other health outcomes including Parkinson disease, amyotrophic lateral sclerosis, and kidney and urinary disorders were also reviewed. THE COMMITTEE'S CONCLUSIONS General Observations Regarding Findings VAO committees classify the evidence regarding exposure to the COIs and health outcomes into four categories: sufficient, limited or suggestive, inadequate or insufficient, and no association.
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Limited or Suggestive Evidence of an Association Epidemiologic evidence suggests an association between exposure to herbicides and the outcome, but a firm conclusion is limited because chance, bias, and confounding could not be ruled out with confidence.b For example, a well-conducted study with strong findings in accord with less compelling results from studies of populations with similar exposures could constitute such evidence. There is limited or suggestive evidence of an association between exposure to the chemicals of interest and the following health outcomes: Laryngeal cancer Cancer of the lung, bronchus, or trachea Prostate cancer Cancer of the urinary bladder *
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There is inadequate or insufficient evidence to determine association between exposure to the chemicals of interest and the following health outcomes that were explicitly reviewed: Cancers of the oral cavity (including lips and tongue) , pharynx (including tonsils)
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. limitations of the epidemiologic evidence reviewed in this report and in previous VAO reports.
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Earlier studies reviewed in previous updates consistently reported increased hypertension with increasing levels of serum dioxin in Vietnam veterans as well as increased prevalence in veterans with higher presumed exposure to the COIs. When considered in light of other new research and earlier studies that demonstrated a consistency in the direction and magnitude of this effect, the committee found that this body of literature constitutes sufficient evidence of an association.
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Thus, a case can be made that the body of literature regarding the exposure to the COIs and diabetes meets the criteria for sufficient evidence of an association, but it was not clear to the committee as a whole whether a category change was appropriate, given its limitations. Findings on Health Outcomes Identified for Special Focus by VA As noted, VA asked the committee to specifically address three health outcomes: possible generational health effects that may be the result of herbicide exposure among male Vietnam veterans, myeloproliferative neoplasms, and glioblastoma multiforme.
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The committee observes that, in general, those studies that have looked at the correlation between exposure to the COIs and hematological outcomes have generated much more compelling results for abnormalities of lymphoid development and immune function, such as non-Hodgkin lymphoma, chronic lymphocytic leukemia, multiple myeloma, and MGUS, than have those that examined myeloid neoplasms of granulocytic lineage such as MPN. Given the absence of new studies, the paucity of epidemiologic studies in general, and the lack of information on the biologic plausibility of a connection between exposures to the COIs and abnormalities of hematopoietic cells, the committee concluded there was inadequate or insufficient evidence of an association between exposure to the COIs and MPN.
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Estimating the magnitude of risk of each particular health outcome among herbicide-exposed Vietnam veterans requires quantitative information about the dose–time–response relationship for the health outcome, information on the extent of herbicide exposure among Vietnam veterans, and estimates of individual exposure. Vietnam veterans were exposed to other agents and stresses -- such as tobacco smoke, insecticides, therapeutics, drugs, diesel fumes, alcohol, hot and humid conditions, and combat -- that may have independent effects or increase or decrease the ability of chemicals in herbicides to produce a particular adverse health outcome.
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Generally speaking, the recommendations of previous VAO committees fell into four primary areas: better management of veterans' health information; additional epidemiologic studies; improvement of exposure estimation; and priority areas for toxicologic research. Suggested future activities included these areas plus initiatives related to the collection and analysis of additional information on Vietnam veterans' service, exposures, and health.
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FINAL OBSERVATIONS In the course of carrying out its Statement of Task, the committee has offered myriad criticisms of the conduct of studies of Vietnam veterans' health, pointing out specific weaknesses and shortcomings in particular papers and widespread (although not universal) issues such as poor exposure characterization, failure to fully control for confounding influences on outcomes, and sample sizes that are inadequate to draw statistically meaningful results.
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