Veterans and Agent Orange Update 2014 (2016) / Chapter Skim
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3 Exposure to the Herbicides Used in Vietnam
3 Exposure to the Herbicides Used in Vietnam
Pages 65-92
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From page 65... ...
The chapter concludes by reviewing several key methodologic issues in human population studies: disease latency, possible misclassification based on exposure, and the exposure specificity required for the scientific evaluation of study results. The exposure of human populations can be assessed in a number of ways, including the use of historical information, questionnaires and interviews, measurements in environmental media, and measurements in biologic specimens.
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From page 66... ...
All of those exposure-assessment approaches have been used in studies of Vietnam veterans. MILITARY USE OF HERBICIDES IN VIETNAM The military use of herbicides in Vietnam took place from 1962 through 1971.
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From page 67... ...
Orange II 50% n-butyl ester of 910 g/L acid After -- Unknown; 2,4-D, 50% isooctyl equivalent 1968 at least ester of 2,4,5-T 3,591,000 L shipped White Acid weight basis: 21.2% By acid 1966– 19,860,108 L 20,556,525 L triisopropanolamine weight, 240 1971 (5,246,502 gal) salts of 2,4-D, g/L 2,4-D, 65 5.7% picloram g/L picloram Blue Cacodylic acid Acid, 65% 1962– -- 25,650 L powder (dimethylarsinic acid)
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From page 68... ...
Herbicides were identified by the color of a band on 55-gallon shipping containers and were called Agent Pink, Agent Green, Agent Purple, Agent Orange, Agent White, and Agent Blue. Agent Green and Agent Pink were used in 1961 and 1965, and Agent Purple in 1962–1965.
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From page 69... ...
EXPOSURE TO THE HERBICIDES USED IN VIETNAM 69 a. Trichlorophenol, the precursor for the synthesis of 2,4,5-T, is formed by the reaction of tetrachlorobenzene and sodium hydroxide (NaOH)
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From page 70... ...
EXPOSURE OF VIETNAM VETERANS Determining the exposures of US military personnel who served in Vietnam has been perhaps the greatest challenge in the study of the health effects associated with herbicides and TCDD. Some military personnel stationed in cities or
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From page 71... ...
. 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 more specific exposure information is not available.
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From page 72... ...
. The exposure index that was initially proposed relied on military spray records for the TCDD-containing herbicides (Agent Orange, Agent Purple, Agent Pink, and Agent Green)
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From page 73... ...
. Blood samples collected from 50 Vietnam veterans in 1996 showed an association between veterans reporting having sprayed herbicides and higher serum TCDD concentrations; this finding was confirmed in a follow-up study of a larger fraction of the cohort (Kang et al., 2006)
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From page 74... ...
was responsible for handling, transport, and storage of herbicides from the time it was delivered to Vietnam until it was loaded onto Ranch Hand aircraft, the herbicide exposures of Allied troops during these procedures may have been negligible. Exposure of Ground Troops In light of the widespread use of herbicides in Vietnam for many years, it is reasonable to assume that many military personnel were inadvertently exposed to the chemicals of concern.
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From page 75... ...
proposed further work on exposure reconstruction and the development of a model that could be used to categorize exposures of ground troops. The committee cautioned that serum TCDD measurements should not be regarded as a "gold standard" of exposure, that is, as a fully accurate measure of herbicide exposure.
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From page 76... ...
Other hot spots that have been identified include depots of chemical defoliants, airbases used for defoliant spray missions, and areas where chemical defoliants were used extensively. The Vietnamese population has since inhabited the areas in and around many former airbases and
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From page 77... ...
Dioxin concentrations in breast milk reflect the residence location of the mothers, with levels and TEQs being elevated in areas where herbicides sprayed during the war and tending to be still higher in areas where herbicides were stored. Phu Cat airbase, a hot spot in South Vietnam, has recently been the focus of several studies examining dioxin levels in human sera and breast milk and corresponding levels of steroid hormones.
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From page 78... ...
Models for Characterizing Herbicide Exposure The development of a means of characterizing the exposure of individual Vietnam veterans has long been a prime objective for use in refining epidemiologic investigations of health outcomes in this population. Serum TCDD levels might have been a very useful proxy for harmful exposures to all the components of the herbicides used by the US military in Vietnam.
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From page 79... ...
. The report concluded that "despite the shortcomings of the exposure assessment model in its current form and the inherent limitations in the approach, the committee agreed that the model holds promise for supporting informative epidemiologic studies of herbicides and health among Vietnam veterans and that it should be used to conduct studies" (p.
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From page 80... ...
(2009a) claim that the resulting estimates are more accurate and more appropriate for estimating aerial herbicide exposure than those from the EOI model because they are quantitative in nature, unlike the EOI model, which was designed to provide rank-ordered exposures.
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From page 81... ...
Additionally, while several field studies have been used to test the modeled ground deposition results of AgDRIFT, there do not appear to have been any tracer or field studies to validate the composite model relating deposition to human exposure estimates. Discrepancies between the modeled AgDRIFT deposition estimates and scores from the EOI model, when applied to similar time points for Vietnam-era exposures, were reported by Ginevan et al.
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From page 82... ...
. Given the lag time since herbicide exposures in Vietnam took place and the lack of direct exposure measurements from that era, it is neither possible to fully validate either the AgDRIFT or EOI models, nor to ascertain the accuracy and precision of estimates from either model or the claims of either Stellman and Stellman (2013)
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From page 83... ...
The survey results showing the distribution of perceived herbicide exposure among the Korean veterans are presented in Table 3-2. These self-reported perceived exposures are not directly comparable to the objective EOI scores, which were designed to assess the exposure opportunity that would result from unintended proximity to herbicide spraying and not the direct result of duties that required handling or applying herbicides (IOM, 2008b)
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From page 84... ...
The Korean investigators obtained locations and calendar date histories for the military units represented in their cohort and provided this information to the Stellman group to use as input to obtain EOI scores from its model, which consolidates all the temporal and spatial information gathered from the original military records on the herbicide spray missions conducted in Vietnam. The investigators classified the resulting EOI scores using two- and four-group categorizations, and multiple aggregations of military units, as summarized in Tables 3-3 and 3-4.
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From page 85... ...
An exposure classification that put only the top 10 or 15 percent in the "high" category would perhaps have been better for the purpose of identifying adverse health effects due to exposure. In summary, the recent Korean study overcame significant logistical challenges in applying the EOI model to a large-scale epidemiologic study of a broad spectrum of health effects.
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From page 86... ...
Given that nondifferential misclassification of exposure would bias measures of association toward the null, observed statistically significant relationships between EOI scores and health effects are likely to be real. METHODOLOGIC ISSUES IN EXPOSURE ASSESSMENT The focus here is on several key methodologic issues that complicate the development of accurate estimates of exposure of the Vietnam-veteran population and the other study populations discussed in this report: The latent period between exposure and disease, exposure misclassification, and exposure specificity.
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From page 87... ...
Despite their continuous nature, however, measurements of serum TCDD levels have decreasing utility for epidemiologic research as they are derived from samples drawn longer and longer after the exposure in question occurred. The variance of the underlying exposed and non-exposed groups has increased to the extent that two overlapping populations can no longer be distinguished, effectively leading to an increase in misclassification.
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From page 88... ...
, Cacodylic Acid, and Picloram Specificity of Exposure Relevance to Committee's Reported in Study Additional Information Charge Pesticides Chemicals of interest were not used, or Not relevant there was no additional information Chemicals of interest were used Limited relevance Herbicides Chemicals of interest were not used Not relevant There was no additional information Limited relevance Chemicals of interest were used Relevant Phenoxy herbicides -- Highly relevant 2,4-D or 2,4,5-T -- Highly relevant Cacodylic acida -- Highly relevant Picloram -- Highly relevant aNone of the epidemiologic studies reviewed by the committee to date has specified exposure to cacodylic acid.
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From page 89... ...
toxic equivalent (TEQs) or concentrations of individual congeners recognized as having dioxin-like activitya TCDD or mixture of Established on the basis of Highly relevant PCDDs environmental sampling or work histories TCDD or mixture of Concentrations in tissues of a subset Very highly relevant PCDDs of participants (preferably soon after exposure)
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From page 90... ...
Among the various chemical classes of herbicides that have been identified in published studies reviewed by the committee, phenoxy herbicides, particularly 2,4-D and 2,4,5-T, are directly relevant to the exposures experienced by US military forces in Vietnam. On the basis of the assumption that compounds with similar chemical structure may have analogous biologic activity, information on the effects of other chemicals in the phenoxy herbicide class -- such as 2-(2,4,5-trichlorophenoxy)
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From page 91... ...
First, the exposure of Vietnam veterans to substantial amounts of the other chemicals, relative to exposure to TCDD, has not been documented. Second, the most important mechanism for TCDD toxicity involves its ability to bind to and activate the AHR.
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