Veterans and Agent Orange Update 2010 (2012) / Chapter Skim
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From page 1... ...
, 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 and some other formulations sprayed in Vietnam; it is important to remember that Agent Orange is not synonymous with TCDD or dioxin. Complaints from returning Vietnam veterans about their own health and that of their children combined with emerging toxicologic evidence of adverse effects of phenoxy herbicides and TCDD in animal studies and some positive epidemiologic studies resulted in sustained controversy.
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From page 2... ...
" the following regarding associations between specific health outcomes and exposure to TCDD and other chemicals in herbicides used by the military in Vietnam: A) whether a statistical association with herbicide exposure exists, taking into account the strength of the scientific evidence and the appropriate ness of the statistical and epidemiological methods used to detect the association; B)
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From page 3... ...
In accord with its charge, the committee examined outcome measures commonly used to evaluate statistical associations, while assessing the adequacy of control for bias and confounding and the likelihood that an observed association could be explained by chance. Additionally, the committee assessed evidence concerning biologic plausibility derived from laboratory findings in cell-culture or animal models.
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From page 4... ...
, the committee remains neutral, abiding by the maxim that "absence of evidence is not evidence of absence." In accord with Congress's mandated presumption of herbicide exposure for 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 obtain information potentially relevant to the evaluation of health effects related to herbicide exposure in addition to that available from studies of Vietnam veterans, the committee reviewed studies of other groups potentially exposed to the constituents of the herbicide mixtures used in Vietnam (2,4-D, 2,4,5-T, TCDD, cacodylic acid, and picloram)
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The committee recognizes that an absolute conclusion about the absence of association might never be attained, because, as is generally the case in science, studies of health outcomes after herbicide exposure cannot demonstrate that a purported effect is impossible, only that it is statistically improbable. EVIDENCE REVIEWED BY THE COMMITTEE The sections below summarize new epidemiologic information evaluated in this update and integrated with that previously assembled.
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From page 6... ...
One study on Army Chemical Corp personnel produced findings related to all cause mortality, while another study on Australian Vietnam veterans evaluated the prevalence of a multitude of self-reported health outcomes, including cancers, circulatory diseases, respiratory diseases, diabetes, and digestive disorders. A third study examined the progression of prostate cancer in a case–control study of veterans with previous Agent Orange exposure.
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From page 7... ...
THE COMMITTEE'S CONCLUSIONS Health Outcomes The present committee weighed the strengths and limitations of the epide miologic evidence reviewed in this report and in previous VAO reports. Although the studies published since Update 2008 are the subject of detailed evaluation in this report, the committee drew its conclusions in the context of the entire body of literature.
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From page 8... ...
Spina bifida in offspring of exposed people 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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From page 9... ...
Neurodegenerative diseases, excluding Parkinson disease Chronic peripheral nervous system disorders Hearing loss (newly addressed health outcome) Respiratory disorders (wheeze or asthma, chronic obstructive pulmonary disease, and farmer's lung)
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bEvidence for an association is strengthened by experimental data supporting biologic plausibility, but its absence would not detract from the epidemiologic evidence.
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From page 11... ...
The committee believes that there is sufficient evidence to reach general or qualitative conclusions about associa tions 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 individu ally. Without information on the extent of herbicide exposure of Vietnam veterans and quantitative information about the dose–time–response relationship for each health outcome in humans, estimation of the risks experienced by veterans exposed to the chemicals of interest during the Vietnam War is not possible.
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From page 12... ...
The committee for Update 2008 concluded that it was plausible that exposure to the herbicides sprayed in Vietnam could cause paternally mediated effects in offspring as a result of epigenetic changes, and such potential would most likely be attributable to the TCDD contaminant in Agent Orange. There is a growing body of evidence that TCDD, and also arsenicals, can induce epigenetic changes in animal models, but there remains extremely limited data on the risk of paternal exposure to xenobiotics in general, and the VAO chemicals of interest in particu lar, resulting in adverse effects on their offspring.
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From page 13... ...
It is the committee's conviction that work needs to be undertaken promptly to resolve questions regarding sev eral health outcomes, importantly COPD, tonsil cancer, melanoma, Alzheimer disease, and paternally transmitted effects to their offspring. Creative analysis of VA's own data resources and further work on cohorts that have already been established may well be the most effective way to address those outcomes and to gain a better understanding of the role of herbicide exposure in development of PD in Vietnam veterans.
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