Levels of 2,3,7,8-Tetrachlorodibenzo- -dioxin (2,3,7,8-TCDD) in adipose tissue of U.S. Vietnam veterans seeking medical assistance

2,3,7,8-Tetrachlorodibenzo- -dioxin (2,3,7,8-TCDD) was detected in an earlier study in adipose tissue of U.S. veterans who were exposed to Agent Orange in Vietnam. The levels appear to be directly related to the intensity of exposure¹. We now report on a group of thirteen Vietnam veterans who were screened for 2,3,7,8-TCDD in adipose tissue. All the veterans had sought medical assistance and some had health effects that may be ascribed to exposure to 2,3,7,8-TCDD. Also included are control patients who were taken from the population of the U.S. 2,3,7,8-TCDD was detected in most of the adipose tissue samples at levels ranging from 2 to 14 ppt. No significant differences in the tissue levels of Vietnam veterans and the other persons were found in this preliminary study.     

Environmental fate and bioavailability of agent orange and its associated dioxin during the vietnam war

BACKGROUND: In 1996, the Committee on the Assessment of Wartime Exposure to Herbicides in Vietnam of the National Academy of Sciences' Institute of Medicine (IOM) issued a report on an exposure model for use in epidemiological studies of Vietnam veterans. This exposure model would consider troop locations based on military records; aerial spray mission data; estimated ground spraying activity; estimated exposure opportunity factors; military indications for herbicide use; and considerations of the composition and environmental fate of herbicides, including changes in the TCDD content of the herbicides over time, the persistence of TCDD and herbicides in the environment, and the degree of likely penetration of the herbicides into the ground. When the final report of the IOM Committee was released in October 2003, several components of the exposure model envisioned by the Committee were not addressed. These components included the environmental fate of the herbicides, including changes in the TCDD content over time, the persistence of TCDD and herbicides in the environment, and the degree of likely penetration of herbicides into the ground. This paper is intended to help investigators understand better the fate and transport of herbicides and TCDD from spray missions, particularly in performing epidemiological studies. METHODS: This paper reviews the published scientific literature related to the environmental fate of Agent Orange and the contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and discusses how this affected the potential exposure to TCDD of ground troops in Vietnam. Specifically, the mechanisms of dissipation and degradation as they relate to environmental distribution and bioavailability are addressed. RESULTS: The evaluation of the spray systems used to disseminate herbicides in Vietnam showed that they were capable of highly precise applications both in terms of concentrations sprayed and area treated. Research on tropical forest canopies with leaf area indices (a measure of foliage density) from 2 to 5 indicated that the amount of herbicide and associated TCDD reaching the forest floor would have been between 1 and 6% of the total aerial spray. Studies of the properties of plant surface waxes of the cuticle layer suggested that Agent Orange, including the TCDD, would have dried (i.e., be absorbed into the wax layer of the plant cuticle) upon spraying within minutes and could not be physically dislodged. Studies of Agent Orange and the associated TCDD on both leaf and soil surface have demonstrated that photolysis by sunlight would have rapidly decreased the concentration of TCDD, and this process continued in shade. Studies of 'dislodgeable foliar residues' (DFR, the fraction of a substance that is available for cutaneous uptake from the plant leaves) showed that only 8% of the DFR was present 1 hr after application. This dropped to 1% of the total 24 hrs after application. Studies with human volunteers confirmed that after 2 hrs of saturated contact with bare skin, only 0.15-0.46% of 2,4,5-T, one of the phenoxy acetic acid compounds that was an active ingredient of Agent Orange, entered the body and was eliminated in the urine. CONCLUSIONS: The prospect of exposure to TCDD from Agent Orange in ground troops in Vietnam seems unlikely in light of the environmental dissipation of TCDD, little bioavailability, and the properties of the herbicides and circumstances of application that occurred. Photochemical degradation of TCDD and limited bioavailability of any residual TCDD present in soil or on vegetation suggest that dioxin concentrations in ground troops who served in Vietnam would have been small and indistinguishable from background levels even if they had been in recently treated areas. Laboratory and field data reported in the literature provide compelling evidence on the fate and dislodgeability of herbicide and TCDD in the environment. This evidence of the environmental fate and poor bioavailability of TCDD from Agent Orange is consistent with the observation of little or no exposure in the veterans who served in Vietnam. Appreciable accumulation of TCDD in veterans would have required repeated long-term direct skin contact of the type experienced by United States (US) Air Force RANCH HAND and US Army Chemical Corps personnel who handled or otherwise had direct contact with liquid herbicide, not from incidental exposure under field conditions where Agent Orange had been sprayed.     

Assessing possible exposures of ground troops to agent orange during the vietnam War: The use of contemporary military records

BACKGROUND: Potential exposure of ground troops in Vietnam to Agent Orange and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) remains controversial despite the passage of 30 years since the Vietnam War. Because of uncertainty over the serum dioxin levels in ground troops at the end of their service in Vietnam, attempts have been made to develop a methodology for characterizing exposure of ground troops in Vietnam to Agent Orange and other herbicides based upon historical reconstruction from military records. Historical information is often useful in evaluating and modeling exposure, but such information should be reasonably accurate, complete, and reliable. METHODS: This paper reviews the procedures and supporting historical information related to the spraying of herbicides in Vietnam. The historical information is classified into two categories: procedural information and operational information. Procedural information covered the process and procedures followed in spraying herbicides from US Air Force fixed wing aircraft (Operation RANCH HAND) in Vietnam, and included approval procedures for spray missions, the criteria required to conduct a mission, the control exercised by the Forward Air Controller and the Tactical Air Control Center and the characteristics of the equipment used to apply the herbicides. Operational information includes data from the RANCH HAND Daily Air Activities Reports, which included geographic locations of specific spray missions, the amount of herbicide sprayed by a specific mission, reports of battle damage to spray aircraft, reports of fighter aircraft support for aerial spray missions, and any comments, such as reasons for canceling a mission. RESULTS: Historical information demonstrates that herbicide spray missions were carefully planned and that spraying only occurred when friendly forces were not located in the target area. RANCH HAND spray missions were either not approved or cancelled if approved when there were friendly forces in the area designated for spraying. Stringent criteria had to be met before spray missions could be approved. The operational information shows that spray missions for both defoliation and crop destruction were conducted in an extremely hostile environment. Heavy 'fighter suppression' with antipersonnel ordnance was used to minimize the impact of hostile ground fire on RANCH HAND aircraft. Procedures were in place that prohibited movement of troops into sprayed areas immediately after a mission due to the possible presence of unexploded ordnance delivered by fighter aircraft supporting RANCH HAND missions. The optimal nature of the spray equipment and application procedures minimized the possibility of significant spray drift. Conclusions. Few friendly troops were sprayed by fixed wing aircraft during Operation RANCH HAND, which delivered 95% of all defoliants used in Vietnam. Similarly, few troops were sprayed during helicopter or surface-based spray operations, which constituted the remaining 5% of defoliants. Detailed policies and procedures for approval and execution of spray missions ensured that friendly forces were not located in the areas targeted for spraying. Fighter aircraft assigned to accompany each spray mission frequently suppressed much of the hostile fire with bombs and other ordnance. Confirmed clearance of the target area was necessary to avoid friendly casualties. Historical records establish that these policies and procedures were strictly followed. Exposure of troops whether from direct spraying or movement through areas recently sprayed was very unlikely. The wartime military records of troop positions and herbicide operations are valuable for some purposes, but have specific limitations in exposure reconstruction. The completeness and accuracy of the geographic data (maps used by RANCH HAND and military ground units) were dependent upon the inherent precision of the map, the accuracy with which it depicted surface features, and the completeness and accuracy of the information on which it is based. Navigation by the crew using visual orientation and reference to the map was the only means that aircrew on spray missions had for establishing their locations. A Forward Air Controller independent of Operation RANCH HAND was present at the location of each spray target immediately before and during spraying operations to verify the target location and ensure that friendly forces were clear of the target area. Anecdotal reports of direct spraying of troops in Vietnam likely reflect the RANCH HAND missions spraying insecticide for mosquito control at regular intervals from March 1967 through February 1972. Outlook. The distribution and levels of serum dioxin in RANCH HAND veterans and the US Army Chemical Corps Vietnam veterans (the unit responsible for helicopter and ground-based spray operations) are distinguishable from typical levels in the population decades after the Vietnam conflict. An exposure model similar to that proposed in the 2003 report of the Institute of Medicine's Committee on 'Characterizing Exposure of Veterans to Agent Orange and Other Herbicides Used in Vietnam' was tested in 1988 by the Centers for Disease Control and Prevention and found to be a poor predictor of absorbed dose of TCDD. Military records during the Vietnam War lack the precision to determine that troops were directly sprayed with herbicides during Operation RANCH HAND, especially given the procedures in place to ensure clearance of friendly forces from the target area and the lack of elevated serum levels of TCDD in ground troops judged to have operated in heavily sprayed areas.     

Chlorinated dibenzo-p-dioxin and dibenzofuran levels in human adipose tissue and milk samples from the north and south of Vietnam

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.     

Serum concentrations of chlorinated dibenzo-p-dioxins and dibenzofurans among former New Zealand trichlorophenol workers

This study examined serum levels of 2,3,7,8-substituted chlorinated dioxins and furans, and 15 PCBs for 346 New Zealand employees who worked at a site that manufactured 2,4,5-trichlorophenol (TCP) and 2,4,5-trichlorophenoxy acetic acid (2,4,5-T). Participants with potential TCP or 2,4,5-T exposures had mean lipid-adjusted 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) levels of 9.9 ng kg⁻¹ lipid compared to 4.9 ng kg⁻¹ for workers with no exposure at the site. Among exposed workers, we found evidence of differences in 2,3,7,8-TCDD levels by department and duties. Workers involved in an accidental release had the highest mean 2,3,7,8-TCDD levels, 37.9 ng kg⁻¹, followed by workers in the trichlorophenol plant, 23.4 ng kg⁻¹. Workers with potential intermittent exposures to 2,3,7,8-TCDD in construction, maintenance, mechanics, and transport had 2,3,7,8-TCDD levels above New Zealand background levels of 3.9 ng kg⁻¹, indicating workplace exposures. Among participants with work history indicating no 2,3,7,8-TCDD exposures, we observed some individuals with 2,3,7,8-TCDD levels above background levels. However, in most cases, these workers reported workplace exposures not recorded on their work histories or held other jobs with the potential for 2,3,7,8-TCDD exposures outside the plant. All other dioxin, furan, and PCB levels were similar among the exposed and unexposed workers.     

Body mass index and serum chlorinated dibenzo-p-dioxin and dibenzofuran levels

Several studies have found that current levels of 2,3,7,8 tetrachlorodibenzo-p-dioxin in serum lipids are related to age with older persons generally having higher levels. To account for this age pattern, reference ranges based on national samples have been established in order to allow determination of background levels for regional studies. In several studies, body mass index (BMI), has also been associated with current 2,3,7,8 tetrachlorodibenzo-p-dioxin levels with increasing body mass index related to increasing levels. We measured lipid-adjusted serum levels for all 2,3,7,8-substituted dioxins and furans in 62 chemical manufacturing workers with chlorophenol exposures and 36 workers without chlorophenol exposures employed at the same location. We then assessed the impact of age and BMI on the serum levels of all these compounds in the presence of other potential confounders. We found that both factors are important independent determinants of serum levels of 2,3,7,8-substituted dioxins and furans. Specifically, age and BMI are both important factors for assessing background levels of 2,3,7,8 tetrachlorodibenzo-p-dioxin, 1,2,3,7,8 pentachlorodibenzo-p-dioxin and the calculated total toxic equivalency. BMI, but not age, is important for assessing background levels of higher chlorinated dioxins and some hexachlorofurans. We conclude that age and BMI are both important considerations when comparing a potentially exposed group to a referent group, or to national norms. Further, age and BMI may also be important in epidemiology studies where back-extrapolation from current dioxin levels is used to assess historical chlorophenol exposure.     

Dioxin contamination in soils of Southern Vietnam

Dioxin is the common name for polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs), and is abbreviated as PCDD/Fs. In the case of Southern Vietnam, is of high concern dioxin contamination in the areas affected by past-use chemical defoliants. Our study related to the zone considered as a "hot spot"--Bien Hoa Airbase and surrounding areas (Bien Hung Lake). Although the war ended over 30 years ago, the adverse effects on this territory still continue. Soil and sediment were selected for our research as they act as a sink for PCDD/Fs. The samples were taken and analyzed in CECOTOX laboratory following certified procedures. The total amounts of PCDD/Fs (2,3,7,8 related congeners) in the samples were converted into WHO-TEQ and compared with standard values proposed by Canadian environmental quality guidelines. The obtained data shows a relatively high risk (up to 20.4 times higher than (probable effect level) PEL value for sediment and 46 times higher than standard value for soil). The research is continuing on the assessment of dioxin transport in food chain. Moreover, considering the obtained data a complete solution should be found urgently to solve the problem of dioxin contamination in the studied areas.     

Blood dioxin biomonitoring to assess local residents' exposure from a large urban remediation project

Background

A total of 265 000 m³ of dioxin contaminated soil and sediments from past industrial activity was treated on site in an urban setting in Sydney, Australia. To respond to local community concerns about potential dioxin exposure from fugitive emissions a human biomonitoring study was undertaken.

Objective

To determine whether local residents were exposed to significant amounts of dioxin from the remediation process.Methods: Blood samples were collected from local residents around the site and a representative metropolitan control group. They were pooled within age and sex strata and the change in dioxin concentrations over the remediation period and a summary of the mid point and post remediation dioxin concentrations were compared between groups. Information on dietary intake was collected to look for possible confounding.

Results

The mean dioxin Toxic Equivalent concentrations (TeQ) decreased among both the local resident and control groups over the remediation period by 1.9 and 2.1 pg gm⁻¹ lipid respectively. Modelled blood concentrations adjusting for age and sex did not detect a significant difference between groups for changes in either TeQ or 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8 TCDD). The summary measure approach did however demonstrate that the 2,3,7,8 TCDD concentrations among the local resident group was approximately 0.7 pg g⁻¹ lipid higher compared to the control group post remediation. There were no significant changes in dietary intake sources of dioxin.

Conclusion

Biomonitoring demonstrated that local residents were not exposed to significant quantities of dioxin. Large scale remediation of dioxin contaminated land can be safely undertaken in an urban setting.     

Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (PCBs) in the serum of US Air Force veterans in 2002

We measured levels of PCDDs, PCDFs, non-ortho, and mono-ortho substituted PCBs in 106 US Air Force Vietnam veterans, participants of the Air Force Health Study (AFHS) who attended the final medical examination in 2002. Twelve veterans were Ranch Hands involved in aerial spraying of herbicides in Vietnam (1962-1971), and 94 were Comparisons who flew transport missions in Southeast Asia (SEA) during the same time period. These veterans had no previous 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) measurement because they had not attended any of the previous AFHS examinations, or their previous measurements were missing or not valid. The mean TCDD levels in 2002 were 1.7 pg/g lipid in Comparisons and 5.5 pg/g lipid in Ranch Hands. The mean PCDD toxic equivalent - TEQ (1997) in Comparisons was 12.6 pg/g lipid, 5.4 pg/g lipid for PCDFs, 5.2 pg/g lipid for non-ortho PCBs, and 9.4 pg/g lipid for mono-ortho PCBs, with a total mean TEQ (1997) of 32.6 pg/g lipid. Corresponding mean TEQs in Ranch Hands were 15.5 pg/g lipid for PCDDs, 4.6 pg/g lipid for PCDFs, 2.2 pg/g lipid for non-ortho PCBs, and 9.3 pg/g lipid for mono-ortho PCBs, yielding the total mean TEQ (1997) of 31.6pg/g lipid. Using the re-evaluated 2005 WHO TEFs, the total mean TEQs (2005) decreased by about 28% in both Comparisons and Ranch Hands, to 23.6 pg/g lipid and 22.8 pg/g lipid, respectively. This was mainly due to changes of TEFs for the group of mono-ortho PCBs, which decreased the mono-ortho PCBs TEQs by almost 90% in both Ranch Hands and Comparisons.     

Long overlooked historical information on agent orange and TCDD following massive applications of 2,4,5-t-containing herbicides,eglin air force base,sFlorida

BACKGROUND: From 1961-1971, The Air Development Test Center, Eglin Air Force Base (AFB), Florida, developed, tested, and calibrated the aerial spray systems used in support of Operation RANCH HAND and the US Army Chemical Corps in Vietnam. Twenty major test and evaluation projects of aerial spray equipment were conducted on four fully instrumented test grids, each uniquely arrayed to match the needs of fixed-wing, helicopter, or jet aircraft. Each of the grids was established within the boundary of Test Area 52A of the Eglin Reservation. METHODS: The tests, conducted under climatic and environmental conditions similar to those in Vietnam, included the use of the military herbicides (Agents) Orange, Purple, White, and Blue. Approximately 75,000 kg of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and 76,000 kg of 2,4-dichlorophenoxyacetic acid (2,4-D) were aerially disseminated on an area of less than 3 km2 during the period 1962-1970. Data from the analysis of archived samples suggested that an estimated 3.1 kg of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), present as a contaminant, were aerially released in the test area. Because most of the vegetation had been removed before establishing the test site in 1961, there was an opportunity to follow ground-based residues independent of canopy interception, and the resulting high solar exposure of initial residues. Studies of the soils, fauna, flora, and aquatic ecosystems of the test grids and associated perimeters of Test Area C-52A (an area totally more than 8 km2) were initiated in 1969 and concluded in 1984. RESULTS AND DISCUSSION: Data from soil samples collected from 1974 through 1984 suggested that less than one percent of the TCDD that was present in soil when sampling began persisted through the ten-year period of sampling. More than 340 species of organisms were observed and identified within the test area. More than 300 biological samples were analyzed for TCDD and detectable residues were found in 16 of 45 species examined. Examination of the ecological niches of the species containing TCDD residues suggested each was in close contact with contaminated soil. Indepth field studies, including anatomical, histological and ultrastructural examinations, spanning more than 50 generations of the Beachmouse, Peromyscus polionotus, demonstrated that continual exposure to soil concentrations of 0.1 to 1.5 parts-per-billion (ng/g) of TCDD, had minimal effects upon the health and reproduction of this species. CONCLUSIONS: Since Agent Orange with its associated TCDD contaminant was aerially disseminated on the test grids, Test Area C-52A provided a 'field laboratory' for what may have happened in Vietnam, had there been no intercepting forest cover. However, in Vietnam a 'typical' mission would have disseminated 14.8 kg of 2,4,5-T/ha, most of which was intercepted by the forest canopy, versus the 876 kg 2,4,5-T/ha on the test grid at Eglin. Moreover, each hectare on the Eglin test grid received at least 1,300 times more TCDD than a hectare sprayed with Agent Orange in Vietnam. The disappearance or persistence of TCDD is dependent upon how it enters the ecosystem. Spray equipment test and evaluations missions at Eglin were generally scheduled and conducted with environmental conditions that were optimal for spray operations. This suggests that conditions favorable for dissemination of herbicide were the same conditions favorable for photodegradation of TCDD. It was likely that 99 percent of the TCDD never persisted beyond the day of application. No long-term adverse ecological effects were documented in these studies despite the massive quantities of herbicides and TCDD that were applied to the site. Reviews by the US Environmental Protection Agency and the National Academy of Sciences' Institute of Medicine did not address the fate of Agent Orange and TCDD as described in these studies from Eglin AFB, Florida.     

Simulation of dioxin accumulation in human tissues and analysis of reproductive risk

Polychlorinated dibenzo-p-dioxin, polychlorinated dibenzofuran and dioxin-like polychlorinated biphenyl concentrations in human liver, kidney, fat, blood, muscle, richly perfused tissue (brain, lung etc.) and skin were simulated to assess the health risk for Japanese fetuses. A 40-year time course of dioxin accumulation via food ingestion was simulated using a physiologically based pharmacokinetic (PBPK) model. In richly perfused tissue, the concentration estimated by the PBPK model showed better agreement with measured concentrations than that calculated by the one-compartment model. Fetal dioxin concentration was simulated based on the assumption that the fetal concentration was almost equal to the concentration in the mother's richly perfused tissue. To assess the reproductive risk, the estimated concentration in human fetus was compared with that in rat fetus in which reproductive function showed signs of alteration by 2,3,7,8-TCDD in previous reports [Toxicol. Appl. Pharmacol. 114 (1992) 118; 146 (1997) 11; Toxicol. Sci. 53 (2000) 411; 57 (2000) 275]. The present daily intake of 2,3,7,8-TCDD is approximately 1/50 of the amount that leads to possible reproductive toxicity in the next generation. However, when 29 kinds of dioxin congeners are considered, the present level is 1/5 of the hazardous levels. For species extrapolation of dioxin risk, further study on tissue concentration versus toxicity is required.     

Abundance and sources of ambient dioxins in Hong Kong: a review of dioxin measurements from 1997 to 2001

Ambient measurements of seventeen 2,3,7,8-polychlorinated dibenzo-p-dioxin/dibenzofuran congeners (2,3,7,8-PCDD/Fs) have been taken in a number of monitoring programs or ad-hoc studies in Hong Kong. The longest monitoring program started at two locations in the territory in July 1997. The other monitoring efforts are ad-hoc studies, varying from a few coordinated sampling events at multiple sites to a year-long monitoring project that targeted suspected local dioxin sources. In this paper, we examined these measurements to understand the ambient levels, temporal and spatial variation, and possible sources of the 2,3,7,8-PCDD/Fs in Hong Kong. The territory-wide annual average concentration of the dioxins was 0.052 pg I-TEQ/m3 measured at the regular monitoring stations in the most recent annual cycle of 2000/2001. This level fell at the lower end of the range of dioxin concentrations measured at other urban locations around the world. The dioxin levels showed a clear seasonality in that elevated concentrations were observed in the winter and lower concentrations in the summer at all monitoring sites with one year or more regular measurements. The measurements indicated that the few known local dioxin sources, including a major chemical waste incinerator facility, landfill sites, and vehicular traffic, are not important contributors to ambient dioxins in Hong Kong. On days of high dioxin concentrations, the 2,3,7,8-PCDD/F congeners were observed to have almost identical compositions with a north-northwest to south-southeast spatial gradient in concentrations at different sampling locations in Hong Kong. This observation, along with other collaborative evidence, established a strong link between high dioxin concentration days in Hong Kong and regional transport of the polluted air masses from the north.     

Perinatal dioxin exposure, cytochrome P-450 activity, liver functions and thyroid hormones at follow-up after 7-12 years

OBJECTIVES: Prenatal and lactational exposure to Dutch "background" dioxin levels may cause health effects spanning many years. In addition, perinatal studies have shown a relationship between dioxin exposure and thyroid disturbance. To assess the later health effects of prenatal and lactational dioxin exposure on liver function we measured plasma ALAT and ASAT levels amongst our longitudinal cohort, as was done perinatally and at 2(1/2) years. The children underwent a caffeine loading test to determine CYP1A2 activity. To assess the later effects on thyroid function we measured plasma TSH and FT4. STUDY DESIGN: A longitudinal cohort of 37 healthy children (age 7-12, mean 8.2 years), with documented prenatal and lactational dioxin exposure, ingested 3mg caffeine/kg BW 6h prior to blood withdrawal. Paraxanthine/caffeine molar ratio, ALAT, ASAT, TSH and FT4 were determined in venous blood. RESULTS: Linear regression of ASAT and ALAT revealed no relation with prenatal and lactational dioxin exposure. No correlation was found between the paraxanthine/caffeine molar ratio and prenatal and lactational dioxin exposure. Linear regression of TSH and FT4 revealed no relation with prenatal and lactational dioxin exposure. CONCLUSION: This follow-up has shown a normalisation of previously abnormal ALAT and ASAT levels, indicating a transient effect. CYP1A2 activity, measured by means of a caffeine-loading test, revealed no correlation with the prenatal and lactational exposures. A normalisation of previously abnormal thyroid hormone homeostasis was seen, also possibly indicating a transient effect. This study provides new data on long-term follow-up after perinatal dioxin exposure to background levels of dioxins.     

Examination of dioxin fluxes recorded in dated aquatic-sediment cores in the Kanto region of Japan using multivariate data analysis

Past dioxin (coplanar polychlorinated biphenyl (Co-PCB), 2,3,7,8-substituted polychlorinated dibenzo-p-dioxin (PCDD) and 2,3,7,8-substituted polychlorinated dibenzofuran (PCDF)) fluxes recorded in dated aquatic-sediment cores were analyzed using principal component analysis (PCA). The data set consisted of samples from four cores collected from the Kanto region of Japan. Time trends and spatial differences in the dioxin flux were examined, and the potential relationship to emission sources was investigated. Twenty-five compounds and 58 core slices, corresponding to the later half of the 20th century, were subjected to the analysis. The PCA of both log-transformed and maximum-value-standardized data successfully divided the dioxin compounds into a small number of groups, and three similar clusters of Co-PCBs, PCDDs and penta- to hepta-CDFs were identified. PCB formulations used in the past are judged to have been responsible for the major part of the Co-PCB flux recorded in the sediment cores. However, the relationship to emission sources needs further investigation. It is suggested that most 2,3,7,8-substituted PCDDs and PCDFs are different from Co-PCBs in their emission sources or movements in the environment. The subcore clusters obtained from the PCA of log-transformed data show that the cores from different sampling areas exhibited distinct dioxin fluxes and compositions. Common time trends among the cores were more effectively summarized by the PCA of maximum-value-standardized data focusing on relative time trends. PC scores show that recently the flux of each dioxin compound in the four cores has been generally declining after having reached a peak.     

Human PCDD/PCDF levels near a pentachlorophenol contamination site in Tainan, Taiwan

A pentachlorophenol (PCP) manufacturing plant in southern Taiwan discontinued production in 1989. The site of the abandoned plant was heavily contaminated by PCDD/PCDFs, impurities formed in the PCP production process. Serum samples collected from 27 residents living near the deserted plant were evaluated to determine whether this contamination had associated serum levels of PCDD/PCDFs in local residents. The average level of 17 tested congeners ranged from 556 to 5240 pg/g lipid (mean, 1670 pg/g lipid). The corresponding 2,3,7,8-TCDD toxicity equivalent quotient values calculated by international toxicity equivalent factors (I-TEFs) and those recommended by WHO (WHO-TEFs) were 47.2 pg I-TEQ/g lipid and 53.4 pg WHO-TEQ/g lipid, respectively. Levels in other parts of Taiwan typically range from 15 to 20 pg WHO-TEQ/g lipid; therefore, it is likely that the heavily contaminated plant site caused these unusually high serum levels. The average PCDD/PCDF levels of 29 fish-tissue and nine soil samples collected from the sea reservoir surrounding the abandoned PCP plant were also abnormally high: 8630 pg/g lipid (985 pg WHO-TEQ/g lipid) and 606000 pg/g-sample (922 pg WHO-TEQ/g-sample), respectively. Factor analysis indicated that the congener pattern of human serum samples collected from residents living near the abandoned PCP plant different from samples collected from other areas in Taiwan without known PCDD/PCDF pollution. Similar results were observed for the fish tissue and soil samples. The current study may have discovered a "hot spot" for elevated dioxin human exposure in Taiwan. The preliminary finding has raised a public health concern in the inspected area and requires further investigations to clarify the nature of the contamination and potential impact on the local environment and human health.     

Dioxin formation in pulp and paper mills of India

Samples of effluents, sludge, pulp, final products (paper) and soil were collected from the identified pulp and paper mills in India. The samples were analysed for 2,3,7,8-tetrachloro-dibenzo-p-dioxin (2,3,7,8-TCDD) and other dioxin congeners and precursors. Pulp and paper mills using chlorine for the bleaching process showed the presence of 2,3,7,8-TCDD in effluent samples. In the effluent and pulp samples from mills where chlorine dioxide was used as a bleaching agent, the 2,3,7,8-TCDD congener ranged from below the detection limit 0.05 to 0.12 ngL⁻¹/ngg⁻¹. The relative standard deviation of reproducibility and the percent recovery of 2,3,7,8-TCDD were 2.07 and 82.4% in pulp and 2.8 and 92% in effluent, respectively. The 1,3,6,8-TCDD was the only other major dioxin congener found in the treated and untreated effluent and sludge samples. However, dichlorobenzene, trichlorophenyl, and hexachlorobiphenyl were detected in all samples. The formation of dioxins can be minimised by replacing chlorine with chlorine dioxide in bleaching processes in pulp and paper mills.     

A novel source for dioxins present in recycled fat from gelatin production

Within a survey on dioxins in animal fat used as feed ingredient, a sample originating from pigs offal was shown to contain 50 ng Toxic Equivalents (TEQ) PCDD/PCDFs kg(-1) fat. Further investigation revealed fat samples with levels as high as 440 ng TEQ kg(-1) fat and contaminated feed with a highest level of 8.4 ng TEQ kg(-1) feed. The congener pattern was dominated by 1,2,3,7,8-PeCDD and 2,3,7,8-TCDD, and was not recognized from any previous incident or known dioxin source. Remarkably, 2,3,7,8-substituted congeners were much more abundant than their non-2,3,7,8-substituted counterparts. The sampled fat was derived from a gelatin production plant. Broken filters, used to clean the hydrochloric acid (HCl) used in the process, caused the dioxin contamination. The fat was primarily used for pig feed. A new physiologically-based pharmacokinetic (PBPK) model for lipophilic contaminants in growing slaughter pigs predicted levels at slaughter varying between 40 pg TEQ g(-1) fat (worst-case) and 2.5-7pgTEQ g(-1) fat under more realistic scenarios. Almost 300 farms were temporarily blocked. Many fat samples of pigs were analyzed using a combined approach of DR CALUX and GC/HRMS. Levels in contaminated pig fat were around the EU-limit of 1 pg TEQ g(-1) fat, with some samples up to 2-3 pg TEQ g(-1) fat. Of 80 negative samples analyzed by DR CALUX and GC/HRMS no false-negatives were obtained, whereas 36 and 62 of the 80 samples classified suspected with the bioassay had GC/HRMS levels above respectively the tolerance and action limits. It is concluded that novel and unexpected dioxin sources remain a threat to the food chain and require the proper evaluation and monitoring of production processes, including chemicals used therein.     

Serum PCDD/F concentration distribution in residents living in the vicinity of an incinerator and its association with predicted ambient dioxin exposure

The aim of this study was to evaluate the serum polychlorinated dibenzo-p-dioxin (PCDD) and dibenzofuran (PCDF) concentration distribution in residents living in the vicinity of an incinerator and its association with annual ambient dioxin exposure predicted by an atmospheric dispersion model. A municipal waste incinerator in Northern Taiwan was chosen for this study. This incinerator had been in operation for 6 years at the time of this study. Using the incinerator site as the center, based on the simulated ambient annual average PCDD/F concentrations. Ninety-five volunteers, all live within a radius of 5 km from the incinerator for at least 5 years, who had no occupational exposure potential, were selected based on the population distribution in each district. The average serum PCDD/F concentration for these subjects living within four zones was about 14 pg I-TEQ/g lipid. The serum distribution levels of people of the four study zones, however, were not consistent with the predicted ambient levels. Results also suggest that ambient exposure might not be the most important contributor to serum concentrations when compared to other exposure sources, such as dietary intake.     

Dispersion modelling of dioxin releases from the waste incinerator at Avonmouth,Bristol, UK

A modified Gaussian atmospheric dispersion model, Industrial Source Complex (ISCST3), is used to estimate toxic equivalent ground level concentrations (GLC) of dioxins emitted from the Avonmouth municipal waste incinerator (MWI) in Bristol, UK. The sensitivity of the predicted GLC to various vapour and particle partitioning scenarios is reported. Predictions incorporating local terrain and actual emission data are used to estimate the mean incremental intake of dioxin due to MWI operation for local residents, through an existing multi-pathway human exposure model. Results are compared with predictions of incremental intake for a generalised MWI. The mean incremental dioxin intake for a hypothetical maximum exposed individual (HMEI) is shown to be up to 46.5% of the background intake compared to only 1.14% for the generalised MWI scenario. This indicates that the use of local terrain and emission data in MWI dispersion modelling is crucial for health risk assessments associated with human dioxin intake, especially in view of the current debate over the tolerable daily intake for dioxins.     

Risk assessment of dioxins and dioxin-like PCBs in food--comments by the German Federal Environmental Agency

Human health risk assessments for dioxins and dioxin-like PCBs (with the exception of the one by US-EPA) recommend health based exposure limits within the range of 1-4 pg WHO-TEQ/kg bw per day. As all humans are exposed to measurable levels of dioxins and related substances, the determination of the tolerated daily intake is a very significant decision and may influence limit values guiding risk reduction measures and target levels. The proposed TDI has to protect all human subpopulations. In the case of dioxin this is particularly important as the exposure of infants through breast-feeding may exceed the exposure of adults by one or two orders of magnitude. An overview of recently recommended limit values (WHO, SCF, JECFA) for PCDDs, PCDFs and dioxin-like PCBs using WHO-TEFs shows the common feature that the values were derived only from non carcinogenic endpoints. In November 2000 the Scientific Committee on Food of the European Commission published an 'Opinion of the SCF on the Risk Assessment of Dioxins and Dioxin-like PCBs in Food' [SCF, Scientific Committee on Food 2000. Opinion of the SCF on the risk assessment of dioxins and dioxin-like PCBs in food. European Commission, Brussels, Adopted on November 2000 http://europa.eu.int/comm/food/fs/sc/scf/out78_en.pdf]. On the basis of this extensive review of data and experimental results the Committee recommended a temporary tolerable weekly intake (t-TWI) of 7 pg WHO-TEQ/kg bw. Only six months later the SCF carried out a re-evaluation of its t-TWI from November 2000. The reconsideration of 'pivotal studies' led to the situation that the re-assessment is now based only on rat studies which investigated only reproductive effects only on male offspring and, in addition, three of these studies are single dose studies at gestational day 15. Applying an overall uncertainty factor of 10 to the LOAEL derived estimated human daily intakes (EHDI) the SCF concluded that 14 pg/kg bw per week should be considered as a tolerable intake for 2,3,7,8-TCDD. The SCF stated that on a body weight basis, the dioxin intake of breast-fed infants has been estimated to be one to two orders of magnitude higher than the average adult intake. Recent German data suggest that the body burden of formerly breast-fed children aged 9-11 is still about 30% higher than those of their formula-fed age-mates. As breast-feeding has measurable benefits for neurological and immunological development, formula feeding cannot be recommended as an alternative to lower dioxin intake. So the only remaining way to lower the dioxin uptake is to drastically reduce the background exposure of the general population. It is acknowledged that any recommendation of a precise number for a TDI is flawed by uncertainties and the possibility of different weight being given to the studies of relevance. The determination of the TDI has influence on all regulatory limit values that are based on the TDI value. A higher TDI lowers the level of protection for humans. It is proposed by the German Federal Environmental Agency that the TDI should be reassessed in a process transparent to the public and on the basis of all relevant endpoints from animal experiments and human epidemiology, including the assessment of cancer risks.