Ranch Hand

There is suggestive but inconclusive evidence of adverse cardiovascular effects in humans exposed to relatively high concentrations of CDDs. ° Increased deaths from chronic heart disease were observed in the Seveso cohort, but psychosocial factors could not be ruled out. No clear dose-response relationships were seen among the Ranch Hand cohort. Increased deaths from heart and circulatory disease were reported among German workers exposed to CDDs. No evidence of adverse cardiovascular effects was observed in US workers. 

Pirkle J et al Estimates of the half-life of 2,3,7,8-tetrachlorodibenzo-p-dioxin in Vietnam veterans of Operation Ranch Hand. 7 Toxicol Environ Health 27 165, 1989... 

Michalck JE et al Pharmacokinetics of TCDD in veterans of Operation Ranch Hand 10 year follow-up. J Toxicol Environ Health 47 209, 1996... 

In its Agent Orange exposure study, the CDC identified 600 Vietnam veterans who had been present at times and in areas near where the Air Force s Operation Ranch Hand had sprayed Agent Orange and compared the concentrations of dioxin in the blood lipids (these concentrations are called body burdens ) of those veterans with the concentrations in some 100 other veterans who had never served in Vietnam. The dioxin concentrations in the exposed and nonexposed veterans were the same, and the concentrations in both groups fell within the concentrations measured in the general population.10... 

The Ranch Hands and Comparisons have undergone week-long physical and psychological examinations at five-year intervals beginning in 1982, with the last examinations begun in the fall of2002. The examinations are carried out in civilian hospitals by physicians and technicians who are not told which men are in the Ranch Hand and which are in the Comparison group. 

The Air Force scientists who direct the Ranch Hand study concluded, in 1997, that dioxin exposure is associated with increased risk of adult-onset diabetes,12 which is the only disease that they link to dioxin. In their most recent comment on the possible dioxin-diabetes link, the Air Force scientists state that the evidence for a connection is weaker in the data collected in the 1997 exams than in the data from the 1992 exams.131 doubt that... 

G. L. Henrikson et al., Serum Dioxin and Diabetes Mellitus in Veterans of Operation Ranch Hand, Epidemiology8 (1997) 252-58. 

J. E. Michalek and N. S. Ketchum, April 25,2002, Diabetes and Dioxin in Air Force Health Study Participants, typescript, 9 pp., prepared for the Department of Health and Human Services advisory committee to the Ranch Hand study. 

At very high doses, such as experienced by a few chemical workers and attempted suicides, herbicides can cause symptoms of acute chemical poisoning. Environmental exposures do not cause such effects, and none was reported in the Ranch Hands. 

In reaching its conclusion about spina bifida, the IOM committee relied primarily on the results from the Ranch Hands. There was no difference in the frequency of all birth defects in the children of Ranch Hands and Comparisons.42 There were, however, four neural tube defects—three cases of spina bifida and one 59... 

W. H. Wolfe et al., Paternal Serum Dioxin and Reproductive Outcomes Among Veterans of Operation Ranch Hand, Epidemiology 6 (1995) 17-22. 

Chance almost certainly explains the difference in the occurrence of the neural tube defects, as it explains many other results in epidemiology. For instance, many early studies of possible effects from exposures to herbicides reported increases in cleft lip and cleft palate (none of which was considered significant)43 among children born to exposed parents. In contrast, there were five cases of cleft lip and cleft palate among the children bom to the Comparisons and none in the children born to Ranch Hands. No one would argue that Agent Orange prevents cleft lip and palate based on this observation. 

Chance is a far more likely explanation for the occurrence of four cases of neural tube defects among the Ranch Hand children as compared to zero cases among the Comparison children, just as it is the most likely explanation for the occurrence of five cleft lip/cleft palate cases among the Comparison children and their absence from Ranch Hand children. The alternative explanation that herbicides cause spina bifida and prevent cleft lip/cleft palate is not at all credible. 

The authors of the Ranch Hand Study, the Department of Health and Human Services committee that reviewed the study before publication,44 the reviewers and editors of the journal Epidemiology that published the study, and a scientist who wrote a comment about the Ranch Hand study for Epidemiology found no support for an association between herbicide exposure and any birth defect. Only the IOM committee identified the biologically implausible association. 

Like the 1996 decision about spina bifida, the IOM committee s conclusion that there is limited/suggestive evidence for an association between herbicide exposure and adult onset diabetes47 draws upon the results from the Ranch Hand study.48 Although the frequency of diabetes among the Ranch Hands and the Comparisons is essentially equal, in 1992, the Air Force showed a video tape to participants in the Ranch Hand heahh study that stated... 

The maximum body burden of dioxin in the Comparisons is 55 ppt (parts per trillion of dioxin in fat taken from a blood sample), about ten times less than the maximum of 618 ppt in the Ranch Hands, but the incidence of diabetes is the same in both populations. The IOM 2000 committee s report about diabetes is masterful. It emphasizes every factoid that can be interpreted to support its conclusion about a limited/suggestive association and brushes aside all the contradictory information. Based on the committee s finding of a limited/suggestive association, the DYA is paying compensation to Vietnam veterans who have diabetes. 

Making reference to a study of U.S. veterans who reported that they had served in Vietnam and to a study of Australian veterans of the Vietnam war, the IOM committee concluded that fathers exposures could increase the occurrence of acute myelogenous leukemia in their children.50 The IOM committee conceded that there is no information about exposure to herbicides in either study, and it ignored the data from the Ranch Hand study, which showed no excess of leukemias during the first eighteen years of the lives of Ranch Hand children. 

It is clear that there is no causative association between dioxin and diabetes because very different levels of exposures to dioxin in the Comparisons and the Ranch Hands are associated with similar frequencies of diabetes. How are those data to be interpreted ... 

Michalek, J.E., J.L. Pirkle, S.P. Caudill, R.C. Tripathi, D.G. Patterson Jr., and L.L. Needham. 1996. Pharmacokinetics of TCDD in veterans of Operation Ranch Hand 10-year followup. J. Toxicol. Environ. Health 47(3) 209-220. 

McAuliffe, A.C., Korea and the Chemical Corps, Ordnance Magazine (1951). McConnell, A., Mission Ranch-Hand, Air University Review, 21 (1970). 

Pirkle, J., Wolfe, W., Patterson, D., Needham, L., Michalek, J., Miner, J., Peterson, M., Phillips, D. (1989) Estimates of the half-life of 2,3,7,8-tetrachlorodibenzodioxin in Vietnam veterans of operation ranch hand. J. Toxicol. Environ. Health 27, 165-171. 

In general, workers involved in the manufacture of 2,4,5-TCP and subsequent products were exposed to far greater levels of 2,3,7,8-TCDD than those involved in the handling and application of chlorinated pesticides containing CDDs. Current serum lipid levels of 2,3,7,8-TCDD in a small number of U.S. Air Force veterans who were directly involved in the aerial spraying of herbicides (Agent Orange contaminated with 2,3,7,8-TCDD) in Vietnam as part of Operation Ranch Hand,... 

TCDD levels using a half-life of approximately 7 years. The 7.1-year half-life was derived from a study of 36 veterans involved in Operation Ranch Hand (Pirkle... 

No respiratory effects were associated with exposure to 2,3,7,8-TCDD-contaminated herbicides in a group of Vietnam Air Force veterans involved in Operation Ranch Hand examined more than 10 years after the war (Wolfe et al. 1985). In the 1987 follow-up (USAF 1991), no association was found between the initial or current serum level of 2,3,7,8-TCDD and incidences of asthma, bronchitis, pleurisy, pneumonia, or tuberculosis abnormal spirometric measurements were often associated with CDD blood levels, but according to the authors (USAF 1991), the differences in the mean level between high- and low-exposure subjects were not clinically important. The authors suggested that these findings may have been related to the association between 2,3,7,8-TCDD and body fat because obesity is known to cause a reduction in vital capacity. 

No cardiovascular effects were observed in a group of Air Force veterans exposed to 2,3,7,8-TCDD-contaminated herbicides during the Vietnam war and examined several years post-exposure (Wolfe et al. 1985). However, a follow-up study of the Ranch Hand cohort reported increased mean diastolic blood pressure in those with current serum lipid 2,3,7,8-TCDD levels from 15 to 33.3 ppt, but not in subjects with higher 2,3,7,8-TCDD serum levels (USAF 1991). In addition, the proportion of abnormally low peripheral pulses in all Ranch Hand veterans, regardless of serum levels, was elevated relative to a comparison group. Also, arrhythmias detected on the electrocardiogram were significantly associated with 2,3,7,8-TCDD exposure, but there was no consistent dose-response relationship. 

A health study of Vietnam veterans involved in Operation Ranch Hand indicated an association between high initial and current serum 2,3,7,8-TCDD levels and increased erythrocyte sedimentation (Wolfe et al. 1995), and an earlier study by Wolfe et al. (1985) indicated an increase in mean corpuscular volume however, these changes were minor and were not observed in the 1991 follow-up (USAF 1991). Higher serum 2,3,7,8-TCDD levels were also associated with positive dose-response trends for increases in white blood cell and platelet levels. 

In a follow-up study, Calvert et al. (1996) examined the association between exposure to 2,3,7,8-TCDD and serum lipids. In the follow-up the authors chose not to adjust the 2,3,7,8-TCDD serum concentrations for total lipids to avoid the problems of interpretation that would arise when adjusting a covariate by the dependent variable. Consequently, the results obtained in this study cannot be compared directly with those from the Operation Ranch Hand study (see below). The median serum 2,3,7,8-TCDD concentration among the workers was 406.6 femtograms/g serum (fg/g) compared with 36.9 fg/g among the referents. 

A health study in Vietnam veterans involved in Operation Ranch Hand found no liver diseases linked to... 

TCDD serum levels (USAF 1991). The diabetes finding remained significant even after adjusting for body fat. Furthermore, subclinical effects in thyroid function (significant decrease in mean T3 uptake and increases in mean TSH) were reported for Operation Ranch Hand veterans with high current... 

The results of a further examination of Operation Ranch Hand veterans was recently published (Burton et al. 1998). The cohort consisted of 930 exposed subjects and 1,200 comparison individuals who served in SEA during the same period but who were not involved with spraying herbicides. The authors examined the associations between serum dioxin levels and a) chloracne, b) occurrence of acne relative to the tour of duty in SEA, and c) anatomical location of acne after service in SEA. Initial dioxin levels were computed using a first-order pharmacokinetic model with a constant half-life of 8.7 years. Four exposure categories were defined 1) comparisons, with current dioxin levels of 10 ppt 2) background Operation Ranch Hand veterans, with current dioxin levels of 10 ppt 3) low category, with current dioxin levels exceeding 10... 

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