Serum Dioxin* in Vietnam-Era Veterans -- Preliminary Report

Agent Orange, a defoliant used in Vietnam, was a mixture of 2,4-DD and 2,4,5-TS. During manufacture 2,4,5-T was contaminated with TCDD*, a compound with marked toxicity in some species of experimental animals (1-4). In 1979, the U.S. Congress responded to concerns of Vietnam veterans by passing Public Law 96-151 mandating epidemiologic studies of the possible health effects on Vietnam veterans of exposure to herbicides and their associated dioxin contaminants. In 1983, CDC developed a protocol (5) for a historical cohort study (the Agent Orange Exposure Study) of U.S. Army veterans who had served in heavily sprayed areas of Vietnam. The protocol specified that the degree of exposure to Agent Orange be based on a score estimating the "likelihood of exposure" and calculated from information in military records.

Men who served in the III Corps military region (around Saigon) during the period 1967-1968 were selected for study because this region was heavily sprayed during that time. The U.S. Army and Joint Services Environmental Support Group (ESG) found that 65 U.S. Army combat battalions had spent at least 18 months in the III Corps area during the period 1967-1968. The ESG abstracted daily locations of companies within these battalions from military records and obtained personnel records of men who had served in those companies. Using existing records of each application of Agent Orange by fixed-wing aircraft, helicopter, or ground-based equipment and ESG troop location data, CDC developed several different methods for computing exposure scores for each man. These methods were based on each man's daily proximity (in time and space) to recorded Agent Orange applications.

Subsequent evaluation of military records by CDC and ESG revealed that daily tracking of individual soldiers was not always possible. The ESG evaluation also suggested that many helicopter and ground-based sprays, which were often near troops, were not recorded. Consequently, CDC has conducted a validation study using current TCDD levels in serum as a biological marker to determine whether scores based on military records or on veterans' self-assessed exposures to herbicides could identify those veterans who had received heavy exposure in Vietnam.

During 1986, CDC's Division of Environmental Health Laboratory Sciences, Center for Environmental Health, developed a method for measuring TCDD in human serum. The measurement, which is based on lipid weight, is highly correlated with paired measurements of TCDD in adipose tissue (r=.98) (6,7). The same laboratory subsequently used paired sera (drawn in 1982 and 1987) to estimate the half-life of the TCDD body-burden in man as approximately 6-10 years (CDC, unpublished data). The sera came from Air Force personnel involved in spraying Agent Orange in Vietnam during 1968. Some of these sera still show markedly elevated TCDD levels in 1987. These new developments suggest that only about 2 to 2.5 TCDD half-lives have elapsed since potential exposure in Vietnam and that serum TCDD can serve as a biological marker for previous Agent Orange exposure. These findings are the basis for the study of U.S. Army veterans reported here.

Vietnam veterans invited to participate in this study had served in at least one of the 65 selected battalions between October 1966 and March 1969. They were chosen from the 9,727 men whose records were sufficiently complete for exposure scoring and who met the original selection criteria proposed in 1983 (e.g., only a single tour of duty in Vietnam and pay grade of E1 to E5 at discharge). The exposure score used to select Vietnam veteran participants was the total number of occasions on which the veteran's unit was within 2 km of a documented Agent Orange spray within 6 days after that spray. This score is based on the assumption that TCDD undergoes rapid degradation on vegetation (8-10). All but 10))P of the 314 men with a high exposure (a score of 5 or more) were invited to participate in this study. A stratified random sample of 235 of the 1,351 men with a score from 1 to 4 were invited, and a sample of 440 of the remaining 8,062, all of whom had a score of 0, were invited. These men averaged over 300 days of service in Vietnam. A stratified random sample of 200 non-Vietnam veterans of the same era were invited as a comparison group. While they did not have Vietnam-related exposure to Agent Orange, their demographic and other personal characteristics were similar to the Vietnam veterans. Of the 979 invited Vietnam veterans, 871 (89) completed telephone interviews, and 665 (68) also completed medical examinations and gave blood for TCDD measurement at CDC. Those reporting health problems in the telephone interview were more likely to participate in the examinations and blood sampling than were those reporting good health. Of the 200 non-Vietnam veterans invited, 103 (52) participated fully. This lower participation rate does not affect exposure scores or TCDD levels in Vietnam veterans. Each participant underwent a detailed interview regarding military and civilian exposures to herbicides. Table 1 shows selected characteristics of the participants by exposure groups. While 25 of Vietnam veterans reported direct exposures (present during spraying or handled spraying equipment) and 70 reported indirect exposure (walked through defoliated areas), 6 of non-Vietnam veterans reported such exposures. Those who were both interviewed and examined were similar with respect to the characteristics shown in Table 1 to those who were interviewed only.

The preliminary TCDD distributions, which are shown in Figure 1 and are based on the first 519 specimens processed, represent a 68 random sample of the participants. All of these men except one had TCDD levels (based on lipid weight) below 20 parts per trillion (ppt), which is considered the upper limit for residents of the United States without known TCDD exposure (6,7,11,12). There was no significant difference among the three Vietnam veteran exposure groups selected on the assumption of short environmental availability of TCDD (p=.83). Likewise, no association was found between TCDD levels and two other methods of scoring exposure that were chosen to reflect a longer environmental persistence of TCDD (one method accounted for the distance from the spray, without regard to the time since spraying, and the other accounted for total days spent in heavily sprayed areas). Finally, no association was found between TCDD levels and self-perceived herbicide exposure in the military (either direct exposure or delayed exposure). The median TCDD levels for all exposure groups were between 3.5 and 4.3 ppt. Furthermore, TCDD medians for Vietnam veterans (median = 3.8 ppt) and non-Vietnam veterans (median = 3.9 ppt) were virtually the same. A full report will be published after TCDD measurements have been completed for all participants and the full report has been reviewed by the Agent Orange Working Group of the Domestic Policy Council (Executive Branch) and by the Congressional Office of Technology Assessment. Reported by: Agent Orange Projects, Div of Chronic Disease Control, Div of Environmental Health Laboratory Sciences, Center for Environmental Health, CDC.

Editorial Note

Editorial Note: The purpose of this study was to determine whether estimates of exposure based on military records or on interviews of U.S. Army veterans can identify those with heavy exposure to TCDD. Serum TCDD levels measured in 1987 were not associated with any of the indirect exposure scoring methods evaluated. Because of the purpose of the study, men with higher exposure scores were deliberately over-sampled. The distribution of TCDD levels reported here cannot be generalized with confidence to all U.S. Army Vietnam veterans since the study did not use a random sample of all such veterans.

While CDC was processing sera from the U.S. Army veterans reported here, it was concurrently processing sera from other groups with known occupational exposure to dioxin prior to but not after 1970. Some of those who were occupationally exposed had TCDD levels more than 30-fold higher in 1987 (CDC, unpublished data) than the median levels of approximately 4 ppt reported here for Vietnam veterans.

The distribution of TCDD levels for the Vietnam veterans, with all but one below the upper limit for unexposed U.S. residents, suggests that few of the participants in this study have had unusually heavy dioxin exposure. No threshold level has been determined as yet for the health effects of TCDD on humans.

References

1. Allen JR, Barsotti DA, Van Miller JP, Abrahamson LJ, Lalich JJ. Morphological changes in monkeys consuming a diet containing low-levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Food Cosmet Toxicol 1977;15:401-10. 2. Norback DH, Allen JR. Biological responses of the nonhuman

primate, chicken and rat to chlorinate dibenzo-p-dioxin ingestion. Environ Health Perspect 1973;5:233-40. 3. Schwetz BA, Norris JM, Sparschu GL, et al. Toxicity of chlorinated

dibenzo-p-dioxins. Environ Health Perspect 1973;5:87-99. 4. Zinkl JG, Vos JG, Moore JA, Gupta BN. Hematologic and clinical

chemistry effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in laboratory animals. Environ Health Perspect 1973; 5:111-8. 5. CDC. Protocol for epidemiologic studies of the health of Vietnam

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