Characterizing Exposure of Veterans to Agent Orange and Other Herbicides Used in Vietnam Scientific Considerations Regarding a Request for Proposals for Research (1997) / Chapter Skim
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APPENDIX
APPENDIX
Pages 12-56
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From page 12... ...
However, because of common background exposures to TCDD, poorly understood variations among individuals in TCDD metabolism, and analytic uncertainty of the analysis, individual TCDD serum levels are usually not meaningful. Furthermore, because not all of the herbicides used in Vietnam contained TCDD, serum TCDD levels are not good indicators of overall exposure to herbicides.
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From page 13... ...
The effect of this bias on risk estimates would likely be to underestimate true effects if they existed, possibly to such an extent that these effects could be missed entirely by future studies. However, it may be possible to develop a valid exposure reconstruction model for epidemiologic studies based on existing records and structured interview data, using principles of historic exposure reconstruction developed by industrial hygienists.
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From page 14... ...
This paper draws on and summarizes material published in chapters 3, 6, and 12 of Veterans and Agent Orange: Health Effects of Herbicides Used in Vietnam and chapter 5 of Veterans and Agent Orange: Update 1996. J ~ r - - r -- ~-c' 7 HERBICIDE USE IN VIETNAM As background for the consideration of measures of exposure to herbicides in Vietnam that can be used in epidemiologic studies of veterans, both the deployment of troops and the military use of herbicides must be considered.
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From page 15... ...
_~^ A ·- ~ ^ ~ ~ ~ ^ ~ ~ _ Military Use of Herbicides in Vietnam From 1962 to 1971, the U.S. Air Force sprayed nearly 19 million gallons of herbicides in Vietnam, of which at least 11 million gallons was Agent Orange, in a military project called Operation Ranch Hand.
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From page 16... ...
The first major operation, to clear enemy infiltration routes, was carried out over the mangrove forests in the Ca Mau peninsula in the southernmost region of the Mekong Delta in September 1962 (Dux and Young, 1980~. Operation Ranch Hand had two primary objectives: (l)
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From page 17... ...
Air turbulence from the aircraft also helped to distribute spray droplets throughout the foliage and was an important factor in the dispersal ofthe spray (MRI, 1967~. Four major herbicide compounds were used in the Ranch Hand herbicide formulations 2,4-D (2,4-dichlorophenoxyacetic acid)
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From page 18... ...
Comparable manufacturing standards for domestic use of 2,4,5-T in 1974 required that TCDD levels be less than 0.05 ppm (NAS, 19744. Therefore, depending on which stocks were sampled, the level of dioxin contamination in Agent Orange could have been up to 1,000 times higher than the level of dioxin found in phenoxy herbicides domestically available at the time.
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From page 19... ...
- i METERS FIGURE A-1. Herbicide spray missions (196~1967)
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From page 20... ...
Units and individuals other than the members of the Air Force Ranch Hand and Army Chemical Corps were also likely to have handled or sprayed herbicides around bases or lines of communication. For example, Navy riverine patrols were reported to have used herbicides for clearance of inland waterways.
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From page 21... ...
Hand spray units consisted of a backpack type of dispenser with a capacity of 3 gallons (Collins, 1967~. Although the Air Force maintained complete records of its Operation Ranch Hand fixed-wing herbicide missions, documentation of spraying conducted on the ground by boat, truck, or backpack and authorized at the unit level was less systematic.
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From page 22... ...
GAO, 1979~. Geographical Distribution of Herbicide Sprays South Vietnam was divided into four combat tactical zones, from I Corps lying south of the DMZ to IV Corps in the Mekong Delta region (Figure A-29.
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From page 23... ...
Army, 19723. The enemy infiltration terminated in base camps within South Vietnam; several were located near the Cambodian border, and others were located near Saigon.
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From page 24... ...
South Vietnam during the Vietnam conflict.
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From page 25... ...
J ~ _ / FIGURE A-3. Herbicide defoliation missions in Vietnam as recorded on HERBS tapes.
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From page 26... ...
estimated that 57 percent of the Rung Sat Special zone had been sprayed. Another heavily sprayed area, the Ca Mau Peninsula at the southern tip of South Vietnam, was almost entirely covered with dense mangrove forests up to 1968.
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From page 27... ...
Also, support troops that operated from major bases might have been exposed because herbicides were used extensively around some base camps to remove tall grasses and heavy growth that obscured visibility. Since herbicides were used around base camps, military personnel could have received exposures in areas where no records of Operation Ranch Hand spraying exist.
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From page 28... ...
When the Ranch Hand cohort was further classified by military occupation, a general increase in serum TCDD levels was detected with jobs that involved more frequent handling of herbicides. The median TCDD level for enlisted ground crew (24 ppt, range 0618 ppt)
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From page 29... ...
Historic exposure reconstruction is a lengthy and expensive process, and the field is still developing. There are, however, some recent examples of occupational epidemiologic studies in which exposure estimates derived from historic reconstruction have proven superior to those relying on simpler measures such as the total duration of exposure (Dement et al., 1983; Stewart et al., 1986; Rinsky et al., 1987; Kriebel, 1988a,b; Seixas, 1990; Blair and Stewart, 19929.
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From page 30... ...
, physical location of the worker during exposure, type of work performed, use of protective equipment, and duration of exposure, the authors could explain 65 percent of the variability in the measured serum TCDD levels. The authors found that estimated back-extrapolated serum TCDD levels were higher in those who experienced severe chloracne (geometric mean = 1,008 ppt, n = 56)
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From page 31... ...
serum TCDD concentration for 397 ground crew was 26 ppt, a quarter of these men had serum TCDD levels above 150 ppt, and some were above 500 ppt. Note that those with the highest exposures had serum TCDD concentrations 20 times greater than the geometric mean.
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From page 32... ...
The proximity of these general unit locations was compared to Agent orange and other herbicide spray data by using the HERBS tapes and other data available on base perimeter sprays to construct the index scores. Approximately 25 percent of interviewed Vietnam veterans reported that they had been exposed to Agent Orange.
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From page 33... ...
This was to be accomplished by determining the proximity of troops to Agent Orange spraying using military records to track troop movement and the HERBS tapes to locate herbicide spraying patterns. The original study was to involve three cohorts, each containing approximately 8,500 men.
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l. Service in selected locations at specific times (any job description except handling Agent Orange)
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From page 35... ...
Self-reported Agent Orange exposure was also determined :! on a number of questions regarding whether subjects had sprayed, loaded, fondled herbicides, or had entered a sprayed area.
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From page 36... ...
The exposure index and the TCDD body More recently, Michalek and colleagues (1995) developed several indices of herbicide exposure for members of the Ranch Hand cohort and tried to relate these to the levels of serum TCDD (see the"Biomarkers" section, below)
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From page 37... ...
A number of other studies, including the Ranch Hand halflife study, the Missouri civilian study, and the NIOSH study, suggest that current serum TCDD levels are useful for distinguishing between groups of individuals that were exposed to TCDD 15 to 20 years ago (CDC, 1989a)
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From page 38... ...
, conducted by the New Jersey Agent Orange Commission, confirmed this result. The pharmacokinetics of TCDD in humans its distribution and passage through the body are not fully understood, which makes individual serum TCDD levels difficult to interpret and also complicates the interpretation of epidemiologic studies relying on these measures of exposure.
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From page 39... ...
If there are group differences in serum TCDD levels, that probably does indicate a difference in exposure to TCDD between the two groups. However, even if there is a difference in TCDD exposure between two groups, it may disappear as subsequent serum levels fade to background levels with the passage of time between exposure and measurement.
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From page 40... ...
. Bearing in mind the limitation of current serum TCDD levels in Vietnam veterans, the AO committee concluded that, with the exception of measured levels in Ranch Hand veterans, exposure to TCDD in Vietnam was substantially less, on average, than that of occupationally exposed workers or of persons exposed as a result of the industrial explosion in Seveso, Italy.
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From page 41... ...
Individual susceptibility to the activity of TCDD seems to vary, especially with respect to the seriousness of the manifestation (Del Corno et al., 1985~. In Seveso, Italy, for instance, after the TCDD release in 1976, approximately half of the adults with the highest serum TCDD levels developed chloracne whereas the other half did not.
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From page 42... ...
It is usually not long lasting, is difficult to diagnose, and is not at all sensitive to exposure to herbicides that are not contaminated with TCDD. CDC Agent Orange Validation Study To test the validity of several indirect methods for estimating exposure of ground troops to Agent Orange in Vietnam, in 1987 the CDC measured serum TCDD lo- els in a nonrandom sample of Vietnam veterans and Vietnam-era veterans who did not serve in Vietnam (CDC, 1988b)
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From page 43... ...
Without adequate knowledge of the decay rate and pharmacokinetics of TCDD in humans, it is not possible to distinguish among these alternative explanations. If initial concentrations of TCDD differed but then over the years fell to background levels, estimates based on reconstruction of troop locations and herbicide spraying activities might be more reliable indicators of exposure than current serum TCDD levels.
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From page 44... ...
veterans. SOURCE: Agent Orange Validation Study (CDC, 1 989a)
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From page 45... ...
This model would incorporate information in existing military records about herbicide spraying (the HERBS and Services HERBS tapes) and troop movements.
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From page 46... ...
Once an exposure reconstruction model has been developed, it should be possible to estimate an exposure score for the large numbers of veterans needed for epidemiologic studies. Ground spraying, although probably representing a smaller quantity of herbicide than aerial spraying, may actually have resulted in heavier human exposures since it probably was done in closer proximity to ground troops, at higher application rates (i.e., number of gallons per acre)
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From page 47... ...
Although the AO committee concluded that group differences can be useful in confirming that exposure measures reflect the differences in prior exposure, the absence of group differences cannot be interpreted to indicate that groups were Serum TCDD measurements should not, therefore, be not exposed earlier. regarded as a gold standard a perfect measure of herbicide exposure.
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From page 48... ...
The task of exposure estimation for a diffuse class of agents to which up to 3 million persons may have been exposed nearly 30 years ago in wartime is inherently difficult. The AO committee recommended that any exposure reconstruction model be thoroughly evaluated before it is used in epidemiologic studies.
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From page 49... ...
1985. Agent Orange Projects Interim Report Number 2: Exposure Assessment for the Agent Orange Study.
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From page 50... ...
1980. Agent Orange: The Bitter Harvest.
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From page 51... ...
1987. Review of Comparison of Serum Levels of 2,3,7,8-TCDD with Indirect Estimates of Agent Orange Exposure in Vietnam Veterans.
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From page 52... ...
1995. Indices of TCDD exposure and TCDD body burden in veterans of Operation Ranch Hand.
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From page 53... ...
1989. Estimates of the half-life of 2,3,7,8-tetrachlorodibenzo-p-dioxin in Vietnam veterans of Operation Ranch Hand.
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From page 54... ...
Comparison of Serum Levels of 2,3,7,8-Tetrachlorodibenzo-p-dioxin with Indirect Estimates of Agent Orange Exposure Among Vietnam Veterans. Atlanta: Centers for Disease Control.
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From page 55... ...
1986. Estimation of exposure to Agent Orange and other defoliants among American troops in Vietnam: a methodological approach.
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From page 56... ...
May 1994. Correlation between dioxin levels in adipose tissue and estimated exposure to Agent Orange in South Vietnamese residents.
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