Objective: The objective of this study was to find sites in Vietnam where there was human exposure from Agent Orange herbicide sprayed between 1962 and 1971, as determined by congener-specific measurement of dioxins, including 2,3,7,8-tetrachlorodibenzodioxin (TCDD), the dioxin that contaminated Agent Orange, in blood. Methods: Blood was collected from residents of eight heavily sprayed regions in the south of Vietnam and analyzed for TCDD and in some cases the dioxin-like dibenzofurans and dioxin-like PCBs. Results: Six of the eight newly studied sites did not show substantial or any elevated TCDD in blood. Marked elevation of TCDD in Vietnamese blood was found in one new location with a suggestion of slightly elevated TCDD in a second location. Conclusions: In newly studied locations in Vietnam, we found some persons with elevation of TCDD consistent with exposure to dioxin from Agent Orange. In our previous studies, we found PCBs, PCDDs, and PCDFs as well as pesticides in human milk, blood, or in food. Health effects from Agent Orange need to be differentiated from effects caused by chemicals other than TCDD from Agent Orange.

Recently, elevated dioxin levels, over 5 parts per trillion (ppt) 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), from Agent Orange was reported in 95% of 43 selected residents of Bien Hoa City, a city in southern Vietnam near a former air base used for Agent Orange-spraying missions. Agent Orange herbicide, contaminated with TCDD, was sprayed in Vietnam between 1962 and 1971 primarily for use as a defoliant. Typical blood TCCD levels are 2 ppt in Vietnamese, but levels are as high as 413 ppt in Bien Hoa City. Elevated TCDD was found in children born many years after Agent Orange spraying ended and in immigrants from non-Agent Orange-sprayed parts of Vietnam, which documented new exposures. Extremely elevated soil TCDD samples, over 1 million ppt, and elevated TCDD in sediment were found in some nearby areas such as Bien Hung Lake. The primary route of intake of almost all dioxins in humans is food. However, in our prior studies in Bien Hoa, food was unavailable for dioxin analysis so the route of intake was not confirmed. In the 1970s, while Agent Orange was still being sprayed, elevated human milk TCDD levels as high as 1850 were detected in milk from Vietnamese people living in Agent Orange-sprayed areas where consumption of fish was high. Furthermore, also in the 1970s, elevated TCDD levels (up to 810 ppt) were found in fish and shrimp from the same area as the milk donors. In the 1980s, we found elevated TCDD and also other organohalogen levels in human tissue, pork, fish, a turtle, and a snake in Southern Vietnam. For these reasons, we recently collected food from Bien Hoa and analyzed it for dioxins, polychlorinated biphenyls (PCBs), DDT and its metabolites, and other organochlorines. We found marked elevation of TCDD, the dioxin characteristic of Agent Orange, in some of the food products, including ducks with 276 ppt and 331 ppt wet weight, chickens from 0.031-15 ppt wet weight, fish from 0.063-65 ppt wet weight, and a toad with 56 ppt wet weight. Usual TCDD levels in food are less than 0.1 ppt. Total TEQ for ducks was from 286-343 ppt wet weight or 536 ppt and 550 ppt lipid; for chickens from 0.35-48 ppt wet weight or 0.95-74 ppt lipid, for fish from 0.19-66 ppt wet weight or 3.2 ppt and 15,349 ppt lipid, and the toad was 80 ppt wet weight and 11,765 ppt lipid. Interestingly, this study did not find elevated levels of TCDD in the pork and beef samples. Clearly, food, including duck, chicken, some fish, and a toad, appears responsible for elevated TCDD in residents of Bien Hoa City, even though the original Agent Orange contamination occurred 30-40 years before sampling. Elevated levels of PCBs and DDT and its metabolites were found in some food samples. Furthermore, measurable levels of hexachlorocyclohexanes (HCH) and hexachlorobenzene (HCB) were found in a wide range of measurable levels. All of the 11 dioxin-like PCBs measured and presented plus 6 dioxins in addition to TCDD and 10 dibenzofurans contributed to the total dioxin toxicity (TEQ). However, when elevated, TCDD frequently contributed most of the TEQ. Thirty-six congeners from 7 classes of chemicals were measured in each of the 16 specimens providing a total of 576 congener levels.

Marked elevation of dioxin associated with the herbicide Agent Orange was recently found in 19 of 20 blood samples from persons living in Bien Hoa, a large city in southern Vietnam. This city is located near an air base that was used for Agent Orange spray missions between 1962 and 1970. A spill of Agent Orange occurred at this air base more than 30 years before blood samples were collected in 1999. Samples were collected, frozen, and sent to a World Health Organization-certified dioxin laboratory fm congener-specific analysis as part of a Vietnam Red Cross project. Previous analyses of more than 2200 pooled blood samples collected in the 1990s identified Bien Hoa as one of several southern Vietnam areas with persons having elevated blood dioxin levels from exposure to Agent Orange. In sharp contrast to this study, our previous research showed decreasing tissue dioxin levels over time since 1970. Only the dioxin that contaminated Agent Orange, 2,3, 7, 8-tetrachlmodibenzo-p-dioxin (TCDD), was elevated in the blood of 19 of 20 persons sampled from Bien Hoa. A comparison pooled sample from 100 residents of Hanoi, where Agent Orange was not used, measured blood TCDD levels of 2 parts per trillion (ppt). TCDD levels of up to 271 ppt, a 135-fold increase, were found in Bien Hoa residents. TCDD contamination was also found in some nearby soil and sediment samples. Persons new to this region and children born after Agent Orange spraying ended also had elevated TCDD levels. This TCDD uptake was recent and occurred decades after spraying ended. We hypothesize that a major route of current and past exposures is from the movement of dioxin from soil into river sediment, then into fish, and from fish consumption into people.

OBJECTIVES:The largest known dioxin contamination occurred between 1962 and 1970, when 12 million gallons of Agent Orange, a defoliant mixture contaminated with a form of the most toxic dioxin, were sprayed over southern and central Vietnam. Studies were performed to determine if elevated dioxin levels persist in Vietnamese living in the south of Vietnam.METHODS:With gas chromatography and mass spectroscopy, human milk, adipose tissue, and blood from Vietnamese living in sprayed and unsprayed areas were analyzed, some individually and some pooled, for dioxins and the closely related dibenzofurans.RESULTS:One hundred sixty dioxin analyses of tissue from 3243 persons were performed. Elevated 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) levels as high as 1832 ppt were found in milk lipid collected from southern Vietnam in 1970, and levels up to 103 ppt were found in adipose tissue in the 1980s. Pooled blood collected from southern Vietnam in 1991/92 also showed elevated TCDD up to 33 ppt, whereas tissue from northern Vietnam (where Agent Orange was not used) revealed TCDD levels at or below 2.9 ppt.CONCLUSIONS:Although most Agent Orange studies have focused on American veterans, many Vietnamese had greater exposure. Because health consequences of dioxin contamination are more likely to be found in Vietnamese living in Vietnam than in any other populations, Vietnam provides a unique setting for dioxin studies.

We previously characterized levels of dioxin and dibenzofuran congeners in adipose tissue and plasma fraction of blood collected from 20 adult males, using paired speciments. It has been found that the 2,3,7,8-TCDD level reported on a lipid basis was similar, although not identical, in plasma lipid and in adipose tissue lipid from the same patients, however, higher levels of the more chlorinated dioxins and dibenzofurans existed in plasma lipid as compared to adipose tissue lipid. This study reports measurements from ten individuals' blood cell fraction and compares this to the plasms fraction and to adipose tissue lipid. In all cases where readily detectable amounts of PCDD/Fs were found, a minimum of 85% was in the plasma fraction and less than 15% in the cellular component. Congeners varied in percentage for each component.

This paper reports general population blood polychlorinated dioxin and dibenzofuran (PCDD/F) levels for various geographical regions in the north and south of Vietnam in pooled samples from 112 persons, the results of 85 individual analyses of blood from Germany, and levels from a pool of whole blood from 100 U.S. residents. This paper also presents selected population data for PCDD/Fs and certain other chlorinated chemicals such as PCBs and other chlorinated xenobiotics in human milk from locations in Vietnam, Cambodia, and Thailand. These represent new samples from seventy persons from the general population from three less industrialized Asian countries; these are compared with our previous findings from several hundred persons from Germany, the Soviet Union, and the United States.

Sixty patients at hospitals in the north and south of Vietnam had adipose tissue dioxin (TCDD only or PCDD/F) analysis performed, 50 as individual TCDD or PCDD/F analyses, and 10 from the north in a pooled sample analysis. Dibenzodioxin and dibenzofuran adipose tissue levels are usually higher in persons from the south of Vietnam than in persons in the north. There is also a direct correlation between human age and PCDD/F levels. However, dibenzofurans, unlike dioxins, do not differ between persons from the north and south of Vietnam. Vietnam provides an opportunity for human health effects studies of PCDD/F exposure.

This paper compares each currently measurable chlorinated dioxin and dibenzofuran congener in fat and blood from 20 human volunteers who are U.S. Vietnam veterans. Our findings confirm previous studies in that 2,3,7,8-TCDD levels in blood and fat tissue are similar, on a lipid basis. However, of other congeners compared, we have found significant differences for some in the levels present in blood to the corresponding levels in fat. The associations between the amount of congener detected in blood and fat for most congeners showed highly significant correlation coefficients.

Chlorinated dioxins and dibenzofurans have been reported in breast milk specimens from a number of countries in recent years. The values reported here extend the number of countries throughout the world from which human milk PCDD/F data is being reported. In general, higher levels of PCDD/Fs are found in industrial areas than in non industrial areas. DDT and its metabolite, DDE, are found in higher levels in milk from Thailand and Vietnam. PCB contamination is highest in milk from Germany, followed by the USA, with Thailand and Vietnam specimens presenting still lower values.

Twenty-seven individual and ten pooled human adipose tissue specimens, collected from persons from the south and north of Vietnam, respectively, were analyzed for 2,3,7,8-TCDD and 2,3,7,8-TCDF. The results show a mean value of 19 ppt TCDD and 7 ppt TCDF in the samples from persons in the South, and non-detected TCDD and TCDF in the samples from persons from the North. Differences in 2,3,7,8-TCDD body burdens continue to be substantiated in the populations of the south and north of Vietnam.

This paper reports that elevated 2,3,7,8-tetrachlorodibenzodioxin (TCDD) adipose tissue levels were found in a subset of U.S. Vietnam veterans. The research is part of a Commonwealth of Massachusetts pilot study to determine if some Vietnam veterans still have elevated 2,3,7,8-TCDD tissue levels as a result of Agent Orange exposure 20 years previously. Measured TCDD levels in this study varied from the low ppt level to 55 ppt. The highest levels were found in veterans who handled the Agent Orange herbicide.

Human milk samples from two highly industrialized countries, Japan and the United States of America, and one developing country, India, were analyzed for dioxins and dibenzofurans. Higher levels of polychlorinated dioxins and dibenzofurans were found in human milk specimens from Japan and the USA than from India. Milk was analyzed from six Japanese women, five from India and two from the United States.

This paper provides a brief review of the human adipose measurements that have been used to estimate exposure to polychlorodibenzodioxins (PCDD) and polychlorodibenzofurans (PCDF). A new study is introduced that focuses on whether 2,3,7,8-tetrachlorodibenzodioxin (2378-TCDD) can still be found in the adipose tissue of U.S. Vietnam veterans. The adipose tissue has been removed by using a refined liposuction technique as an outpatient or office medical procedure. Preliminary data on levels of 2378-TCDD in tissue of U.S. Vietnam War veterans, including 6 members of the Operation Ranch Hand group, are presented and show that some Ranch Handers still carry as much as 40 to 60 parts-per-trillion 2378-TCDD in their adipose tissue whereas other veterans still show little evidence of elevated levels of 2378-TCDD.

PCDDs and PCDFs were determined in samples of human milk collected in 1973 and 1985 in the south of Vietnam and the levels compared to samples taken in 1970 and present day North American samples. In the Vietnam samples from the three time periods between one-half and two-thirds were positive for 2,3,7,8-TCDD. Average levels of the positives on a lipid basis, declined from about 484 ppt in 1970, to 121 ppt in 1973 and then to 12 ppt in 1985. The latter value is higher but similar to the value of about 5 ppt presently found in North American human milk and much higher than that found in samples from the north of Vietnam where Agent Orange was not used. The average body burden of 2,3,7,8-TCDD in the nursing mothers from 1970 and 1973 has been estimated to be 3.6 and 0.98 micrograms, respectively. Such an accumulation is near the value calculated by us to produce chloracne and other symptoms in some industrial workers.

Although 2,3,7,8-TCDD has been found to be extremely toxic to a variety of laboratory aminals, human epidemiology studies, where exposure to 2,3,7,8-TCDD has been less well characterized than in animal toxicologic studies, have been less conclusive in characterizing the extent of toxicity. In order to determine whether the newly refined techniques of human adipose tissue biopsy including isomer specific and sensitive measurement of PCDDs and PCDFs might be able to assist in finding populations within the same country with high and low levels of dioxins, adipose tissue samples were taken and levels analyzed from the north and south of Vietnam. It seemed reasonable, based on previous work, that high levels of 2,3,7,8-TCDD might still be found in adipose tissue in selected patients living in areas sprayed with Agent Orange and other 2,3,7,8-TCDD containing herbicides, and that lower levels should be found in patients not exposed to 2,3,7,8-TCDD from herbicides or other sources, such as persons who had always resided in the north of Vietnam. Of 9 specimens from patients hospitalized in Hanoi who had never been south, none had detectable adipose tissue levels of 2,3,7,8-TCDD at a detection limit of 2 or 3 ppt on a wet weight basis. Of 15 specimens from Ho Chi Minh City hospitalized patients the mean of positive specimens (12 of 15) was 28 on a lipid basis. The mean of the positive values from the south is about 2 to 3 times higher than found in the North American Continent control patients where the mean is about 6–10 ppt and much higher than in the north of Vietnam. In the northern specimens, the levels were non-detectable with a sensitivity of between 2 and 3 ppt. Other PCDD and PCDF isomers not found in Agent Orange, the penta- through octachlorinated dibenzo-dioxins and dibenzofurans, were similar in isomer type and quantity in the south of Vietnam to what we previously reported in North America. Adipose tissue from the north of Vietnam contained the lowest levels of four through eight chlorinated dioxins and furans thus far reported. The initial data suggests that populations exist in the south of Vietnam with elevated levels of 2,3,7,8-TCDD at the present time, fourteen years after the last known 2,3,7,8-TCDD (Agent Orange) application, superimposed on a preexisting body burden of dioxins and dibenzofurans from sources other than Agent Orange such as technical grade pentachlorophenol or products of incineration contaminated with higher chlorinated PCDDs or PCDFs. In light of the recent finding that unexpected levels of PCDDs and PCDFs exist in the general adult population of industrialized countries, ca. 1,000 to 1,200 ppt, wet weight of total dioxin and furan isomers in adipose tissues, it seems reasonable that the extent of human toxicity of dioxins may be more readily characterized in Vietnam than in industrialized countries. Because 2,3,7,8-TCDD was applied in 1962–1970, although not yet cleaned up, the levels of 2,3,7,8-TCDD in the environment, the food chain, and in humans, would be expected to decrease with time. Therefore, if studies are not initiated in a timely fashion, the opportunity to better characterize the extent of the toxicity of TCDD to humans as well as the persistence of TCDD in the environment in Vietnam may be lost.