Characterization of dioxin exposure in firefighters, residents, and chemical workers in the Irkutsk Region of Russian Siberia.

The goal of this study was to characterize body burdens of polychlorinated dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) in three groups of Siberians living in the Irkutsk Region of Russia. These groups included firefighters exposed to a mixture of toxic substances extinguishing a large fire at the Shelekhovo Cable Factory in 1992, chemical workers from the Khimprom chemical plant, and residents living in proximity to large chemical factories in Sayansk and Angarsk. Blood samples from all groups were obtained in the fall of 1998. Dioxin analyses of samples were performed in Germany, Canada, and in a Russian dioxin laboratory in Ufa, Bashkortostan Republic. The average levels of dioxin toxic equivalents (TEQs) are 23.6 parts per trillion (ppt) total TEQ (PCDD/F only) in the disabled firefighters, 25.0 in the non-disabled firefighters, 28.7 in residents, and 45.6 in the Khimprom workers blood. Two workers did have elevated total TEQs of 91.4 and 102.2 ppt. Dibenzofurans and coplanar PCBs substantially contribute to the total elevated TEQ seen here. The average TEQs suggest levels of dioxin exposure in this part of the former Soviet Union not dissimilar to levels measured in industrialized countries of Europe and Northern America.

Levels of dioxins and dibenzofurans in breast milk of women residing in two cities in the Irkutsk Region of Russian Siberia compared with American levels.

The presence of dioxins, dibenzofurans, and polychlorinated biphenyls (PCBs) in human tissue, food, and environmental samples from Russia has been monitored since 1988 as part of a research collaboration between a number of countries including Finland, the United States, Germany, the former Soviet Union, and Canada. Although elevated TCDD and PnCDD levels have previously been found in blood of male and female Russian chemical manufacturing workers and in their children, dioxin levels in the general population have usually been found to be lower than in Americans and Europeans. This study continues earlier work in the Irkutsk region of Russian Siberia, where we report levels of dioxin, dibenzofurans, and PCBs in human milk samples taken from general population women living in the industrialized cities of Angarsk and Usolye-Sibirskoye, near Lake Baikal. Total polychlorinated dibenzo-p-dioxin (PCDD) toxic equivalents (TEQs) compared in this paper for the industrialized regions of Siberia, Ukraine, and the US are similar, ranging from 6.1 to 7 parts per trillion (ppt). Recent 1998 milk samples from Angarsk and Usolye-Sibirskoye have total mean polychlorinated dibenzofuran (PCDF) TEQs of 10 and 21.7 ppt, respectively, with the other industrialized countries ranging from 2.3 to 6.7 ppt. Although dioxin-like PCBs were not measured for the city of Usolye-Sibirskoye (1998), total mean PCDD/F TEQ from Angarsk and Usolye-Sibirskoye (1998) were the two highest levels in this study, with 26.9 and 28.5 ppt, respectively, followed by 1993-1994 Ukraine samples with 24 ppt, 1989 Siberian samples with 13.6 ppt, and 1996 USA with 11.4 ppt total TEQ. In this study, higher levels of dioxins are noted in milk from Angarsk and Usolye-Sibirskoye than found in earlier Russian studies, with mean levels also exceeding 1996 and 1999 US breast milk dioxin levels.

HIV envelope gp120 activates human arterial smooth muscle cells.

There have been increasing reports of acute coronary thrombotic events in patients with HIV. Although these clinical events have been attributed primarily to dyslipidemia associated with protease inhibitor therapy, autopsy studies in children with HIV suggest the presence of an underlying arteriopathy. This study demonstrates that the HIV envelope protein, gp120, activates human arterial smooth muscle cells to express tissue factor, the initiator of the coagulation cascade. The induction of tissue factor by gp120 is mediated by two biologically relevant coreceptors for HIV infection, CXCR4 and CCR5, and is also dependent on the presence of functional CD4. Induction of tissue factor by gp120 requires activation of mitogen-activating protein kinases, activation of protein kinase C, and generation of reactive oxygen species, signaling pathways that have protean effects on smooth muscle cell physiology. The activation of smooth muscle cells by gp120 may play an important role in the vascular, thrombotic, and inflammatory responses to HIV infection.

Intake of dioxins and related compounds from food in the U.S. population.

The first U.S. nationwide food sampling with measurement of dioxins, dibenzofurans, and coplanar, mono-ortho and di-ortho polychlorinated biphenyls (PCBs) is reported in this study. Twelve separate analyses were conducted on 110 food samples divided into pooled lots by category. The samples were purchased in 1995 in supermarkets in Atlanta, GA, Binghamton, NY, Chicago, IL, Louisville, KY, and San Diego, CA. Human milk also was collected to estimate nursing infants' consumption. The food category with highest World Health Organization (WHO) dioxin toxic equivalent (TEQ) concentration was farm-grown freshwater fish fillet with 1.7 pg/g, or parts per trillion (ppt), wet, or whole, weight. The category with the lowest TEQ level was a simulated vegandiet, with 0.09 ppt. TEQ concentrations in ocean fish, beef, chicken, pork, sandwich meat, eggs, cheese, and ice cream, as well as human milk, were in the range O.33 to 0.51 ppt, wet weight. In whole dairy milk TEQ was 0.16 ppt, and in butter 1.1 ppt. Mean daily intake of TEQ for U.S. breast-fed infants during the first year of life was estimated at 42 pg/kg body weight. For children aged 1-11 yr the estimated daily TEQ intake was 6.2 pg/kg body weight. For males and females aged 12-19 yr, the estimated TEQ intake was 3.5 and 2.7 pg/kg body weight, respectively. For adult men and women aged 20-79 yr, estimated mean daily TEQ intakes were 2.4 and 2.2 pg/kg body weight, respectively. Estimated mean daily intake of TEQ declined with age to a low of 1.9 pg/kg body weight at age 80 yr and older. For all ages except 80 yr and over, estimates were higher for males than females. For adults, dioxins, dibenzofurans, and PCBs contributed 42%, 30%, and 28% of dietary TEQ intake, respectively. DDE was also analyzed in the pooled food samples.

Recent dioxin contamination from Agent Orange in residents of a southern Vietnam city.

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 for 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-tetrachlorodibenzo-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.

Exposure of Russian phenoxy herbicide producers to dioxins.

Russian workers who manufactured phenoxy herbicides and related compounds in the 1960s in the city of Ufa, Bashkortostan, a republic of the former Soviet Union, were studied for exposure to polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans. Sixty whole blood samples were drawn in September 1992 and analyzed by gas chromatography-mass spectrometry. Thirty-four workers who manufactured the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) had median blood lipid 2,3,7,8-tetrachlorodibenzo-p-diozin (TCDD) concentrations of 166 ng per kg (parts per trillion) and 1,2,3,7,8-pentachloro-p-dioxin (PnCDD) levels of 52 parts per trillion with several TCDD values greater than 500 ng/kg. These 1992 values are 10 to 30 times greater than contemporary normal or background blood levels from the Baskortostan region of Russia and were at least 10-fold higher 25 years earlier in the late 1960s. Six workers who produced the herbicide 2,4-dichlorophenoxyacetic acid also had elevated levels in 1992, with 1,2,3,7,8-PnCDD blood lipid levels higher than 2,3,7,8-TCDD. Even children of some of the workers and factory administrative personnel had blood levels of TCDD higher than most general population groups from other parts of Russia or from other countries. The patterns of the PCDDs and dibenzofurans (as defined by the specific congeners and their relative amounts) were distinctive for the type of chemical produced, with notable contributions to the TCDD toxic equivalents from the 2,3,7,8-TCDD and 1,2,3,7,8-PnCDD congeners. No correlation was found between chloracne status in 1965 to 1967 and TCDD or toxic equivalent blood lipid concentrations in 1992. These Russian phenoxy herbicide and related chemical producers have some of the highest occupational exposure to dioxins of any cohort studied to date and seem to be unique with respect to the presence of appreciable amounts of 1,2,3,7,8-PnCDD.

Correlations among human plasma levels of dioxin-like compounds and polychlorinated biphenyls (PCBs) and implications for epidemiologic studies.

In studies of the potential health effects of background-level exposure to organochlorine compounds (e.g., polychlorinated biphenyls, polychlorinated dibenzodioxins, and polychlorinated dibenzofurans), investigators have often measured either polychlorinated biphenyls or polychlorinated dibenzodioxins/polychlorinated dibenzofuransbut not both. We measured polychlorinated biphenyls (including specific non-, mono-, and di-ortho congeners) and specific polychlorinated dibenzodioxins/dibenzofurans among 63 Canadian blood donors. Levels of these compounds were, in general, fairly correlated. For example, Pearson's correlation coefficient between log total polychlorinated biphenyl and log total polychlorinated dibenzodioxins was .52. These results suggest that in epidemiologic studies of health effects of background-level exposures to these compounds, the quantitative dose-response relation observed for a given compound (or class of compounds acting through a similar mechanism) may easily be miscalibrated or confounded.

Release of active tissue factor by human arterial smooth muscle cells.

Tissue factor (TF), the initiator of coagulation, is thought to function predominantly at the cell surface. Recent data have suggested that active TF is present extracellularly in atherosclerotic plaques, the arterial wall, and the blood. This study was conducted to determine whether smooth muscle cells (SMCs), a major source of arterial TF, could generate extracellular TF. Active TF accumulated in the medium of cultured human SMCs, representing approximately 10% of that measured in the underlying cells at 24 hours. Platelet-derived growth factor, phorbol ester, and tumor necrosis factor-alpha caused approximately 3-fold increases in TF activity in the medium. Release of TF into the medium was dependent on the presence of the TF transmembrane domain but not the cytoplasmic domain. Antibodies to TF precipitated most of the activity from the culture medium, whereas antibodies to the beta(1)-integrin subunit precipitated approximately 33% of the activity. Treatment with detergent or phosphatidylserine:phosphatidylcholine did not increase activity, suggesting that all TF released by SMCs was in the appropriate lipid milieu and not encrypted. Western blotting showed that the medium contained full-length TF protein. Fluorescent cytometry showed that extracellular TF was present largely in particles < or =200 nm, which had a density of 1.10 g/mL. We hypothesize that active extracellular TF found in the injured arterial wall and atherosclerotic plaques derives, in part, from SMC microparticles.

Levels of methyleugenol in a subset of adults in the general U.S. population as determined by high resolution mass spectrometry.

We developed a sensitive and accurate analytical method for quantifying methyleugenol (ME) in human serum. Our method uses a simple solid-phase extraction followed by a highly specific analysis using isotope dilution gas chromatography-high resolution mass spectrometry. Our method is very accurate; its limit of detection is 3.1 pg/g and its average coefficient of variation is 14% over a 200-pg/g range. We applied this method to measure serum ME concentrations in adults in the general U.S. population. ME was detected in 98% of our samples, with a mean ME concentration of 24 pg/g (range < 3.1-390 pg/g). Lipid adjustment of the data did not alter the distribution. Bivariate and multivariate analyses using selected demographic variables showed only marginal relationships between race/ethnicity and sex/fasting status with serum ME concentrations. Although no demographic variable was a good predictor of ME exposure or dose, our data indicate prevalent exposure of U.S. adults to ME. Detailed pharmacokinetic studies are required to determine the relationship between ME intake and human serum ME concentrations.

Human vascular smooth muscle cells possess functional CCR5.

CC chemokine receptors are important modulators of inflammation. Although CC chemokine receptors have been found predominantly on leukocytes, recent studies have suggested that vascular smooth muscle cells respond to CC chemokines. We now report that human smooth muscle cells express CCR5, a co-receptor for human immunodeficiency virus. CCR5 mRNA was detectable by RNA blot hybridization in human aortic and coronary artery smooth muscle cells. The cDNA generated by reverse transcription-polymerase chain reaction from aortic smooth muscle cells had 100% identity throughout the entire coding region with the CCR5 cloned from THP-1 cells. By immunohistochemistry, CCR5 and the CCR5 ligand, macrophage inflammatory protein-1beta (MIP-1beta), were detected in smooth muscle cells and macrophages of the atherosclerotic plaque. In smooth muscle cell culture, MIP-1beta induced a significant increase in intracellular calcium concentrations, which was blocked by an antibody to CCR5. In addition, MIP-1beta caused a calcium-dependent increase in tissue factor activity. Tissue factor is the initiator of coagulation and is thought to play a key role in arterial thrombosis. These data suggest that human arterial smooth muscle cells express functional CCR5 receptors and MIP-1beta is an agonist for these cells.

Regulation of the procoagulant response to arterial injury.

The last few years have provided increasing evidence to support a major role for TF in the initiation and propagation of thrombosis after acute arterial injury. Although thrombotic occlusion occurs in a small minority of patients undergoing acute coronary interventions or bypass surgery, mural thrombi are likely to be present in almost all cases. These thrombi may stimulate SMC and promote the development of intimal hyperplasia and luminal narrowing. The use of inhibitors of TF and factor VIIa, therefore, may not only be valuable for inhibiting thrombus formation associated with acute arterial interventions, but may also have benefit in attenuating intimal hyperplasia. Although this paper focuses on the role of TF in establishing a procoagulant state after arterial injury, the fibrinolytic system undoubtedly plays a role in balancing the effects of increased TF production in the arterial wall. This is underscored by the success of activators of fibrinolysis (tissue plasminogen activator, streptokinase, urokinase) in revascularization in the setting of acute myocardial infarction and is reviewed elsewhere. Likewise, local regulation of TFPI in the atherosclerotic plaque and injured vessel wall may be important in attenuating the effects of increased TF synthesis and accumulation. It has been assumed that the primary source of active TF after arterial injury is either SMC or invading macrophages and that active TF is anchored to the surface of these cells. Recent data have suggested that the majority of cell-associated TF is either encrypted on the cell surface or present in an intracellular pool. Arterial injury may, therefore, involve the de-encryption of surface TF or the release of intracellular TF. In addition, active vascular TF may be present in microparticles that are not anchored to the arterial wall and may be washed into the circulation. The procoagulant state may be further accentuated by the accumulation of bloodborne TF at sites of arterial injury and in developing thrombi. This TF is likely to arise from circulating leukocytes, including neutrophils and monocytes. These studies suggest that the cellular processing of TF may be an important target for inhibiting thrombotic complications associated with arterial injury and acute coronary events.

Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and coplanar polychlorinated biphenyls in breast milk from two cities in Ukraine.

Substantial environmental pollution has been alleged in Ukraine, but little information is available to allow an assessment of the possible impact on humans. To help remedy this lack of information, it was of interest to investigate whether certain polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), or coplanar polychlorinated biphenyls (PCBs) were elevated in people from Ukraine. Samples of breast milk were obtained from 200 women from the cities of Kyiv and Dniprodzerzhinsk; Kyiv is the capital and Dniprodzerzhinsk is a highly industrialized city. The samples were combined into four pools by city and age, and analyzed for 7 PCDDs, 10 PCDFs, and 2 coplanar PCBs (126 and 169). The total of the measured PCDDs, expressed as toxic equivalent, ranged from 5.1 to 7.6 pg/g lipid; for PCDFs from 3.6 to 5.2, and for PCBs from 11 to 18 pg/g lipid. Results from the two cities were similar; older women had slightly higher concentrations than did younger women. Levels of these compounds seen in Ukraine were similar to or lower than those seen in other recent studies from European and Asian countries.

Correlations among polychlorinated biphenyls, dioxins, and furans in humans.

BACKGROUND: Correlations among human levels of polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans potentially complicate interpretation of studies of their individual health effects. Outcomes attributed to one may, in fact, be due to another. METHODS: We present correlations among dioxins, furans, and PCBs in blood collected in 1991-1992 from 44 American Vietnam veterans from Michigan. RESULTS: Correlations among specific dioxins and furans ranged from 0.26 to 0.80, with the higher-chlorinated congeners being more highly correlated. Correlations among PCBs ranged from 0.06 to 0.94, with those occurring at highest concentrations being more highly correlated. Correlations of PCBs with dioxins and furans ranged from -0.09 to 0.59. Correlations of individual chemicals with total dioxin toxic equivalents ranged from 0.31 to 0.76. DISCUSSION/CONCLUSIONS: If confirmed in other populations, such correlations may allow the use of simpler assays but may also raise issues of confounding and calibration.

A comparison of dioxins, dibenzofurans and coplanar PCBs in uncooked and broiled ground beef, catfish and bacon.

The primary source of dioxins (PCDDs), dibenzofurans (PCDFs) and coplanar PCBs for the general population is food, especially meat, fish, and dairy products. However, most data on the levels of these chemicals is from food in the raw or uncooked state. We report here the effect of one type of cooking (broiling) on the levels of PCDDs, PCDFs, and coplanar PCBs in ground beef (hamburger), bacon and catfish. Samples of hamburger, bacon, and catfish were broiled and compared to uncooked samples in order to measure changes in the amounts of dioxins in cooked food. The total amount of PCDD, PCDF, and coplanar PCB TEQ decreased by approximately 50% on average for each portion as a result of broiling the hamburger, bacon and catfish specimens. The mean concentration (pg TEQ/kg, wet weight) of PCDDs, PCDFs, and coplanar PCBs, however, remained the same in the hamburger, increased by 83% in the bacon, and decreased by 34% in the catfish. On average, the total measured concentration (pg/kg) of the congeners of PCDDs, PCDFs, and coplanar PCBs increased 14% in the hamburger, increased 29% in the bacon, and decreased 33% in the catfish.

Concentrations of PCBs, PCDFs and PCDDs in the blood of Yusho patients and their toxic equivalent contribution.

Yusho blood and control serum were collected in around 1991 and analyzed for congeners of PCDDs, PCDFs and PCBs. In Yusho blood, TEQ was mainly contributed by 2,3,4,7,8-penta-CDF (77-248 ppt), 1,2,3,4,7,8-hexa-CDF (15-37 ppt) and 2,3,3',4,4',5-hexa-CB (16-77 ppt). Total TEQ in Yusho blood (185-441 ppt) was only 3-14 times higher than that of control serum (31-61 ppt). It is notable that the concentrations of 3,3',4,4',5-, 2,3,3',4,4'- and 2,3',4,4',5-penta-CBs in Yusho blood were comparable to or lower up to 3-5 times than those in control blood.

Decrease in levels and body burden of dioxins, dibenzofurans, PCBS, DDE, and HCB in blood and milk in a mother nursing twins over a thirty-eight month period.

This paper presents measured dioxin, dibenzofuran, PCB, DDE and HCB blood and milk levels and estimated body burdens in a mother who nursed twins for thirty-eight months. A total of thirteen milk samples and three blood samples were collected and analyzed. Measured PCDD and PCDF levels in milk decreased from 309 and 21 ng/kg (ppt) to 173 and 9 ng/kg, respectively, between March 1993 and September 1995. Based on the decrease in breast milk dioxin levels, we estimate that the nursing mother reduced her dioxin body burden from 310 to 96 ng dioxin toxic equivalents (TEQs), or approximately 69%. In two and one half years the level of HCB in the mother's milk decreased from 10.7 to less than 1.8 ng/g (ppb), the level of DDE decreased from 246 to 46 ng/g and the total level of non-coplanar PCBs decreased from 285 to 63 ng/g, on a lipid basis. We estimate that the twin's consumption of dioxins, dibenzofurans, and coplanar PCBs from breast feeding was approximately 115 ng TEQ per twin.

Partitioning of dioxins, dibenzofurans, and coplanar PCBS in blood, milk, adipose tissue, placenta and cord blood from five American women.

Partitioning of dioxins, dibenzofurans and the dioxin-like coplanar PCBs was determined by congener-specific high resolution gc-ms analysis of compounds in 6 tissue samples each from 5 women. Samples were whole blood obtained prior to delivery; maternal adipose tissue, cord blood and placenta obtained during cesarean section delivery; and whole blood and milk taken at the time of first obstetrical follow-up examination, one to two months following delivery. All women lived in upstate New York. Specimens were collected in late 1995 and early 1996. Mean measured levels of total PCDDs, PCDFs and coplanar PCBs were 352 pg/g for adipose tissue, 526 pg/g for predelivery blood, 182 pg/g for placenta, 165 pg/g for cord blood, 352 pg/g for postpartum blood and 220 pg/g for milk. Mean total TEQ levels were 11.6 pg/g TEQ for adipose tissue, 12.1 pg/g TEQ for predelivery blood, 10.5 pg/g TEQ for placenta, 5.8 pg/g TEQ for cord blood, 10.0 pg/g TEQ for postpartum blood and 10.2 pg/g TEQ for milk.

Human exposure assessment and the National Toxicology Program.

The National Institute of Environmental Health Sciences/National Toxicology Program (NIEHS/NTP) is developing a new interagency initiative in exposure assessment. This initiative involves the NIEHS, the Centers for Disease Control and Prevention through its National Center for Environmental Health, the National Institute for Occupational Safety and Health, the EPA, and other participating institutes and agencies of the NTP. This initiative will benefit public health and priority setting in a number of ways. First, as discussed above, it will strengthen the scientific foundation for risk assessments by the development of more credible exposure/response relationships in people by improving cross-species extrapolation, the development of biologically based dose-response models, and the identification of sensitive subpopulations and for "margin of exposure" based estimates of risk. Second, it will provide the kind of information necessary for deciding which chemicals should be studied with the limited resources available for toxicological testing. For example, there are 85,000 chemicals in commerce today, and the NTP can only provide toxicological evaluations on 10-20 per year. Third, we would use the information obtained from the exposure initiative to focus our research on mixtures that are actually present in people's bodies. Fourth, we would obtain information on the kinds and amount of chemicals in children and other potentially sensitive subpopulations. Determinations of whether additional safety factors need to be applied to children must rest, in part, upon comparative exposure analyses between children and adults. Fifth, this initiative, taken together with the environmental genome initiative, will provide the science base essential for meaningful studies on gene/environment interactions, particularly for strengthening the evaluation of epidemiology studies. Sixth, efficacy of public health policies aimed at reducing human exposure to chemical agents could be evaluated in a more meaningful way if body burden data were available over time, including remediation around Superfund sites and efforts to achieve environmental justice. The exposure assessment initiative is needed to address public health needs. It is feasible because of recent advances in analytical technology and molecular biology, and it is an example of how different agencies can work together to better fulfill their respective missions.

Quantitation of the extracellular domain of epidermal growth factor receptor in the plasma of dioxin-exposed individuals.

Animal models suggest that dioxins have a negative effect on the level of expression of the epidermal growth factor receptor in cells. In vivo the level of expression in tissue of the epidermal growth factor receptor can be monitored by assaying for the extracellular domain in blood using an enzyme linked immunosorbent assay. We have determined the levels of the extracellular domain of the epidermal growth factor receptor in the plasma of 30 individuals: 10 with high blood dioxin levels (TEQ range = 318-673 ppt), 10 with medium blood dioxin levels (TEQ range = 16-60 ppt), and 10 with low background blood dioxin levels (TEQ range = 3-10 ppt). The levels of the epidermal growth factor receptor extracellular domain were lower in the high blood dioxin group (mean +/- SD = 45 +/- 26 fmol/ml) and the medium blood dioxin group (mean +/- SD = 41 +/- 23 fmol/ml) compared with the low blood dioxin group (mean +/- SD = 73 +/- 43 fmol/ml). These results suggest that the extracellular domain of the epidermal growth factor receptor may be a marker of the biological effect of dioxin exposure.

A selective historical review of congener-specific human tissue measurements as sensitive and specific biomarkers of exposure to dioxins and related compounds.

Estimating internal exposure or dose of dioxins and related chemicals such as dibenzofurans and dioxinlike polychlorinated biphenyls is relatively straightforward in laboratory animals because a known dose is given and the amount absorbed can be measured. In wildlife, direct tissue measurement and measurement of environmental samples have both recently been used to estimate exposure. Until recently, human studies used only indirect indicators such as skin lesions to qualitatively estimate exposure to these chlorinated organic compounds. Environmental measurements have also sometimes been used to estimate human exposure. Dioxins in human tissue were not measured until the 1970s, when 2,3,7,8-tetrachlorodibenzo-p-dioxin was measured in mothers' milk; congener-specific measurement of dioxins and dibenzofurans in tissues (blood, milk, and adipose tissue) of the general population and exposed workers was first performed in the United States in the 1980s. Measurement in a sensitive and specific fashion of the 17 toxic dioxin and dibenzofuran congeners currently found in human tissue from industrial countries began in the 1980s. The use of known chemical standards, capillary columns, high resolution gas chromatography and mass spectrometry (GC-MS) has now become relatively common. GC-MS analysis of blood is currently accepted as the gold standard for estimating human exposure to dioxins. However, analyses are still costly and time consuming, and worldwide there are few qualified laboratories. There is currently a lack of knowledge concerning kinetics at higher and lower exposure levels for most of the toxic dioxin congeners and of levels in target tissues of concern.