[Occurrence and relevance to health of persistent organic substances and phthalates in breast milk]. / Vorkommen und gesundheitliche Bedeutung von persistenten organischen Substanzen und Phthalaten in der Muttermilch.

The aim of this study is to give an overview of the concentrations of persistent organic pollutants like the polychlorinated dibenzo- P-dioxins (PCDD), polychlorinated dibenzofurans (PCDF), polychlorinated biphenyls (PCB), polybrominated diphenyl ether (PBDE), perfluorinated compounds (PFC) and of phthalates in breast milk. On the basis of median and 95 (th) percentile values an "average" and a "high" intake were calculated for a 3-month-old infant exclusively breast-fed. Moreover, the actual daily intake was compared with tolerable daily intakes (TDI) recommended by scientific institutions. On this basis, we found an "average" ("high") daily intake of 70 (140) pg TEQ/kg body weight (b. w.) for PCDD/F and dioxin-like PCB (dl-PCB), 10 (20) ng/kg b. w. for PFOS (perfluorooctanesulfonate), 20 (50) ng/kg b. w. for PFOA (perfluorooctanoate), 1.7 (7.5) ng/kg b. w. for BDE 47, and 0.6 (2.1) ng/kg b. w. for BDE 99. For di-2-ethylhexyl phthalate (DEHP) and di- N-butyl phthalate (DnBP) an "average" and "high" intake of 400 ng/kg b. w. and 2,000 ng/kg b. w. and of 100 and 500 ng/kg b.w. were assumed, respectively. For all of these substances we found a daily intake via breast milk below the TDI, established on a livelong basis. On contrary, the daily intake for the sum of the PCDD/F and dl-PCB considerably exceeded the recommended TDI value. Even with regard to the "high" daily intake values the share of PBDE, PFC, and phthalates on the TDI was only in the lower percentage. Scientific organisations assume that an exceeding of the PCDD/F and dl-PCB intake in relation to the TDI value is acceptable only on the basis of the still declining levels in breast milk and the fact that this high exposure only occurs during some months of the entire life when breast milk is consumed. On the basis of the recent exposure situation mothers can exclusively breast-feed their infants for 6 months without any hesitation. The well established health benefits for mothers and infants when exclusively breast-feeding should be utilised. There is also no health concern if the mother decides to breast-feed the baby for longer than 6 months when the infant also receives additional food.

The Saccharomyces cerevisiae CDC25 gene product binds specifically to catalytically inactive ras proteins in vivo.

Genetic data suggest that the yeast cell cycle control gene CDC25 is an upstream regulator of RAS2. We have been able to show for the first time that the guanine nucleotide exchange proteins Cdc25 and Sdc25 from Saccharomyces cerevisiae bind directly to their targets Ras1 and Ras2 in vivo. Using the characteristics of the yeast Ace1 transcriptional activator to probe for protein-protein interaction, we found that the CDC25 gene product binds specifically to wild-type Ras2 but not to the mutated Ras2Val-19 and Ras2 delta Val-19 proteins. The binding properties of Cdc25 to Ras2 were strongly diminished in yeast cells expressing an inactive Ira1 protein, which normally acts as a negative regulator of Ras activity. On the basis of these data, we propose that the ability of Cdc25 to interact with Ras2 proteins is strongly dependent on the activation state of Ras2. Cdc25 binds predominantly to the catalytically inactive GDP-bound form of Ras2, whereas a conformational change of Ras2 to its activated GTP-bound state results in its loss of binding affinity to Cdc25.

Evaluation of dioxin-like chemicals in pooled human milk samples collected in Australia.

DESIGN: Human milk samples were collected and analysed for the levels of polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and selected dioxin-like polychlorinated biphenyls (PCBs). In total, 157 individual samples collected during 2002 and 2003 as well as 24 samples collected in 1993 were analysed as 20 pools. RESULTS: PCDDs, PCDFs and dioxin-like PCBs were detected in all pooled samples. For samples collected during 2002/2003, the TEQ(DFP) ranged from 6.0 to 15.2 pg TEQ g(-1) lipid with an average of 9.0 pg TEQ g(-1) lipid. The average lipid content was 3.7+/-0.5%. No systematic differences were observed in the levels of PCDDs, PCDFs and PCBs in human milk samples collected from different regions of Australia during 2002/2003. For samples collected in 1993 and analysed as pools, the mean level, expressed as TEQ(DFP) was 16+/-1.4 pg TEQ g(-1) lipid. The average lipid content was 3.9+/-0.7%. CONCLUSION: The levels of PCDDs, PCDFs and dioxin-like PCBs in the human milk of Australian women are both low compared to international levels and similar across all regions of Australia. Consistent with world-wide trends, the levels of PCDDs, PCDFs and dioxin-like PCBs have decreased over a 10 year period from 1993 to 2003 by approximately 40%.

Proteasome inhibitor induced gene expression profiles reveal overexpression of transcriptional regulators ATF3, GADD153 and MAD1.

The ubiquitin/proteasome pathway has been implicated in a wide variety of cellular processes and the number of substrates degraded by the proteasome is impressive. Most prominently, the stability of a large number of transcription factors is regulated by ubiquitination. To elucidate pathways regulated by the proteasome, gene expression profiles were generated, comparing changes of mRNA expression of 7900 genes from the UniGene collection upon exposure of cells to the proteasome inhibitors Lactacystin, Lactacystin-beta-lactone or MG132 by means of microarray based cDNA hybridization. The three profiles were very similar, but differed significantly from a gene expression profile generated with the histone deacetylase inhibitor Trapoxin A, indicating that the observed alterations were indeed due to proteasome inhibition. Two of the most prominently induced genes encoded the growth arrest and DNA damage inducible protein Gadd153 and the activating transcription factor ATF3, both transcription factors of the CCAAT/enhancer binding protein (C/EBP) family. A third gene encoded for the transcriptional repressor and c-Myc antagonist Mad1. Our results suggest that proteasome inhibition leads to upregulation of specific members of transcription factor families controlling cellular stress response and proliferation. Oncogene (2000).

Protein isoaspartyl methyltransferase protects from Bax-induced apoptosis.

Protein L-isoaspartyl methyltransferase (Pimt) is a highly conserved enzyme utilising S-adenosylmethionine (AdoMet) to methylate aspartate residues of proteins damaged by age-related isomerisation and deamidation. We have been particularly interested in this enzyme since addition of the compound CGP3466 to primary rat astroglia cell cultures resulted in an upregulation of Pimt at the mRNA level, as shown here by semi-quantitative RT-PCR. CGP3466 is a compound related to the anti-Parkinson's drug R-(-)-deprenyl, which has been shown to protect from neural apoptosis induced by trophic factor withdrawal [Tatton et al., 1994. J. Neurochem. 63, 1572]. The pro-apoptotic gene Bax is required in the cascade of events following withdrawal [Deckwerth et al., 1996. Neuron 17, 401]. We therefore investigated whether Pimt overexpression was able to affect Bax-induced apoptosis in primary mouse cortical neurons. Our results show that Pimt is indeed able to protect from Bax-induced apoptosis. Furthermore, this activity is not restricted to brain-specific cell types, since the same effect is also demonstrated in COS1 cells. In addition, mutational analysis suggests that the protective effect is dependent on the adenosine methionine-binding motif, which is well conserved in protein methyltransferases, and that a mutation destroying this motif crucially affects cytoskeletal structures of the cell.

The interaction between the catalytic A subunit of calcineurin and its autoinhibitory domain, in the yeast two-hybrid system, is disrupted by cyclosporin A and FK506.

The Ca(2+)-calmodulin dependent protein phosphatase, calcineurin, is thought to mediate the action of the two immunosuppressants, cyclosporin A (CsA) and FK506. Calcineurin from all species consists of a catalytic A subunit and a regulatory peptide B, which plays an essential role in catalysis. The enzymatic function is probably also regulated by an autoinhibitory domain (AID) present in the catalytic subunit. We have used the yeast two-hybrid system to show that the putative AID of the yeast catalytic subunit Cna1 binds only to truncated Cna1, devoid of AID. Although deletion of the genes encoding the yeast catalytic subunits of calcineurin (CNA1 and CNA2) maintain the interaction, absence of the regulatory subunit Cnb1 prevents binding. Interestingly, both CsA and FK506 disrupt this interaction, whereas binding of Cna1 to calmodulin remains unaffected. This indicates that a simple cellular system, developed in yeast, could provide further insight into an understanding of calcineurin inhibition.

Absorption and metabolism of genistin in the isolated rat small intestine.

Uptake and intestinal metabolism of physiologically active genistin were studied in an ex vivo intestinal perfusion model; luminally applied concentrations were 5.9, 12.0, and 23.8 micromol/l. The intestinal absorption of genistin was 14.9% (+/-2.3, n=9), irrespective of the amounts applied. The majority of the absorbed genistin appeared as genistein glucuronide (11.6%), also recovered as the main metabolite on the luminal side (19.5%). Minor amounts of genistin (1.3%) and genistein (1.9%) were found on the vascular side, whereas 15.4% of applied genistin was luminally cleaved to yield genistein. Sulfate derivatives of genistein or genistin were not observed.

Improved analysis of malondialdehyde in human body fluids.

The widely used TBA assay for lipid peroxidation was modified to minimize artefactual oxidative degradation of lipids during the assay. Formation of the TBA-MDA condensation product was studied with and without exclusion of oxygen, and the concentration effect of BHT addition was examined. Oxygen was depleted from the reaction mixture by extensive argon gassing. Exclusion of oxygen resulted in decreased TBARS production in plasma but not in standard solutions. High BHT concentrations resulted in a similar effect. At concentrations higher than 3 mmol/l BHT exclusion of oxygen had no additional effect. By measuring n-butanol extracts in a multititer plate reader this modified method was made suitable as a preliminary screening assay of human body fluids for lipid peroxidation.

Metabolic studies with keto acids in uremia.

The utilization of a preparation containing the keto analogues of five essential amino acids was evaluated by nitrogen balance studies in five uremic patients receiving an 18 g protein diet. In all five patients the nitrogen balance improved when the diet was supplemented with ketoacids, becoming positive in three cases, and about zero in one case. In two cases the improvement in nitrogen utilization occurred without a prior period of adaptation with the protein-poor diet. The nitrogen balance was negative in two cases when reinvestigated after about 7 weeks, but one of these cases had a slight infection at the time of the study.

Plasma free amino acid concentrations in healthy Guatemalan adults and in patients with classic dengue.

BACKGROUND: Plasma free amino acid patterns in health and disease have been reported. However, amino acid concentrations in adult populations in developing countries and in patients with dengue, as a model for an acute infectious viral disease endemic to the tropics, have not been reported. OBJECTIVE: The purpose of this study was to determine the amino acid profile in both healthy Guatemalan adults from different socioeconomic backgrounds and at 3 time points during the course of classic dengue. DESIGN: The study was carried out in Guatemala and included measurement of plasma free amino acids in 22 healthy control subjects (14 low income, 8 middle class) and 17 febrile patients. Measurements of amino acids were repeated within a 48-h interval in 20 of the healthy Guatemalans. In 9 patients with dengue, amino acids were assayed 3 times: on admission to a local hospital in the coastal plain of Guatemala, on hospital discharge, and 7 d after hospital discharge. RESULTS: Branched-chain amino acid concentrations in healthy adults and dengue patients in Guatemala were lower than normal values reported in the literature for healthy Swedish adults. With the exception of increased phenylalanine concentrations and an increased ratio of phenylalanine to tyrosine, all amino acids as well as the Fischer molar ratio were decreased in the acute phase of dengue. CONCLUSIONS: Healthy Guatemalans have different amino acid patterns than do Swedish subjects independent of socioeconomic status. The systemic viral disease dengue is associated with changes in the plasma free amino acid pattern, reflecting infection-related alterations in amino acid metabolism.

Determination of glutamine in muscle protein facilitates accurate assessment of proteolysis and de novo synthesis-derived endogenous glutamine production.

BACKGROUND: Results of tracer studies indicate that skeletal muscle contributes to approximately 70% of overall glutamine production in healthy adults; the contribution of de novo synthesis being estimated at approximately 60%. However, measurement of the de novo synthesis rate in muscle tissue requires knowledge of the appearance rate of glutamine in plasma and the quantity of glutamine derived from intracellular proteolysis. Thus, the content of glutamine in muscle protein is a prerequisite for an accurate calculation. OBJECTIVE: The objective of the study was to measure glutamine in muscle protein. DESIGN: Muscle specimens (open biopsies) were obtained from humans (10 men and 4 women), rats (n = 4), cows (n = 4), and pigs (n = 4). Glutamine was assessed via prehydrolysis derivatization, rapid microwave-enhanced acid hydrolysis, and 5-dimethylaminonaphthalene-1-sulfonyl chloride (dansyl chloride) reversed-phase HPLC, and expressed per mg alkali-soluble protein (ASP) and DNA. RESULTS: Glutamine concentrations in muscle cell protein of various species ranged from 41 to 49 microg/mg ASP; the differences were not species related. The combined means (+/-SDs) for the 4 species were 43.6 +/- 4.9 microg/mg ASP and 11.9 +/- 2.0 mg/mg DNA, respectively. In humans, there was no apparent influence of age, sex, or BMI. CONCLUSIONS: Direct and specific measurements of glutamine in intact muscle protein were 50% lower than assumed previously. We used data compiled from earlier studies to recalculate the contributions of proteolysis and de novo synthesis to the endogenous production of glutamine in selected age groups of healthy humans; these contributions remained remarkably constant at approximately 13% and approximately 87%, respectively.

Clinical relevance of L-carnitine-supplemented total parenteral nutrition in postoperative trauma. Metabolic effects of continuous or acute carnitine administration with special reference to fat oxidation and nitrogen utilization.

Carnitine-free total parenteral nutrition (TPN) is claimed to result in a carnitine deficiency with subsequent impairment of fat oxidation. The present study was designed to evaluate the possible benefit of carnitine supplementation on postoperative fat and nitrogen utilization. Sixteen patients undergoing total esophagectomy were evenly randomized and received TPN without or with L-carnitine supplementation (74 mumol.kg-1.d-1) during 11 postoperative days. On day 11, a 4-h infusion of L-carnitine (125 mumol/kg) was performed in both groups. The effect of supplementation was evaluated by indirect calorimetry, N balance, and repeated measurements of plasma lipids and ketone bodies. Irrespective of continuous or acute supplementation, respiratory quotient and fat oxidation were similarly maintained throughout the study in both groups whereas N balance appeared to be more favorable without carnitine. We conclude that carnitine-supplemented TPN does not improve fat oxidation or promote N utilization in the postoperative phase.

Gastric emptying in humans: influence of different regimens of parenteral nutrition.

Intravenous administration of nutrients can suppress oral food intake. Inhibition of gastric emptying (GE) is a potential explanation for this process. Inhibition of GE during parenteral nutrition (PN) and attenuation of this by parenteral nutrition enriched with branched-chain amino acids (BCAAs) was examined in nine healthy males maintained on standard liquid diets for 6 d before each of three GE studies. GE was measured by scintigraphy after ingestion of a liquid test meal, at weekly intervals, after a 6-h infusion of Ringer lactate solution (RL), peripheral PN, or PN with half the amino acids replaced with BCAAs (BCPN). With PN, gastric emptying during the first 50 min was delayed by 38% compared with RL infusion; BCPN attenuated the effect, suggesting that postabsorptive control of food intake may act through changes in GE. These findings have clinical potential to reduce interference with appetite and to optimize food intake during PN administration.

Biochemical changes associated with severe trauma.

The effects of different intravenous nutritional regimens on a number of biochemical indices of nutritional status were studied during the 8-day period following severe trauma. The inclusion of large amounts of amino acids (high nitrogen (N) was shown to greatly improve N balance over an isocaloric regimen containing no amino acids (O g N). The concentration of serum albumin, transferrin, prealbumin, and retinol-binding protein all fell during the study period in both patient groups, whereas the serum concentrations of acute phase reactants and of ribonuclease increased in the two groups. The sum of plasma levels of branched-chain amino acids and the essential amino acids was increased to a greater extent in the high N group. These amino acid totals and the ratio of glycine/valine showed a significant correlation with N balance in this group. Despite the marked difference in N balance, 3-methylhistidine excretion was increased but equal in the two nutritional groups, suggesting an increased rate of muscle protein breakdown in both groups, which appears not to be influenced by amino acid nutrition. It is concluded that N balance can be significantly improved in the immediate posttrauma period by provision of amino acids together with energy substrates. None of the biochemical variables measured, with the exception of plasma levels of essential amino acids, reflected these marked differences in N balance.

Essential amino acids in the treatment of advanced uremia: twenty-two months' experience in a 5-year-old girl.

The value of conservative treatment in a case of chronic advanced renal failure was investigated in a 5-year-old girl with congenital hypoplastic kidneys. Before treatment the patient was severely anorexic and her plasma urea nitrogen was 180 mg/100 ml. Protein restriction alone was fruitless. After a transitional period on total parenteral therapy the patient was put on a maintenance oral diet, where an energy-rich diet was supplemented with essential amino acids including histidine. Plasma urea nitrogen dropped and stayed at about 50 mg/100 ml during the whole treatment in spite of a rising plasma creatinine from 10 to 24 mg/100 ml. The general condition of the patient normalized as she went into an anabolic state with weight gain and growth in height. The nitrogen balance studied in two different periods was positive. An acute attack of pancreatitis, secondary to hyperparathyroidism, ended the patient's life after 22 months of treatment.

Glutamate concentration in plasma, erythrocyte and muscle in relation to plasma levels of insulin-like growth factor (IGF)-I, IGF binding protein-1 and insulin in patients on haemodialysis.

Elevated insulin-like growth factor binding protein (IGFBP) levels, including IGFBP-1, occur in renal failure, and may contribute towards reduced IGF bioactivity in uraemia. The reduced IGF bioactivity may, in turn, contribute towards the disturbances in protein metabolism present in renal failure. In this study, the relationships between intra- and extracellular amino acid (AA) levels and IGF-I and/or IGFBP-1 levels were studied in 30 adult patients (aged 24-70 years) on haemodialysis who had no clinical signs of malnutrition. Blood samples (n = 30) and muscle biopsies (n = 13) were collected for determination of free AA in erythrocytes (RBC), plasma and muscle by reverse-phase HPLC while IGFBP-1, IGF-I and insulin plasma levels were determined by radioimmunoassay The patients on haemodialysis had elevated glutamate concentrations in RBC and plasma compared with healthy controls (524 +/- 26 vs 448 +/- 17 mumol/l, P < 0.05 and 45 +/- 4 vs 32 +/- 4 mumol/l, P < 0.01 respectively), although glutamate levels in muscle were within the normal range. The mean IGF-I level was slightly increased (s.d. score +0.74 +/- 0.30) but insulin levels were within the normal range. IGFBP-1 levels, which were inversely correlated to insulin (r = -0.40, P < 0.02), were elevated threefold compared with controls. No plasma AA level displayed a significant correlation with IGF-I, IGFBP-1 or insulin levels. However, glutamate concentrations in RBC were positively correlated to IGFBP-1 (r = 0.51, P < 0.01) and inversely correlated to IGF-I (r = -0.46. P < 0.01), although unrelated to insulin. Muscle glutamate, which was inversely related to RBC glutamate, displayed an opposite pattern with an inverse relation to IGFBP-1 levels (r = - 0.73, P < 0.01) and a positive correlation to IGF-I levels (r = 0.64, P < 0.02). Glutamate was the only AA to display an inverse correlation between RBC and muscle (r = -0.65, P < 0.02, n = 12). These findings lead us to propose that, in uraemia, the elevated IGFBP-I levels, which reduce the bioavailability of IGFs, are linked to glutamate uptake in muscle, resulting in accumulation of RBC glutamate. Whether there is a causal relationship or the correlation is due to some common regulator is not clarified in the present study.

Intestinal absorption of rutin in free and conjugated forms.

Quercetin is one of the most common flavonoids in nature, occurring mainly in glycosidic forms such as rutin. Rutin has been reported to exert numerous biochemical and pharmacological activities, though information about its absorption and metabolism is scarce. The aim of this study was to investigate intestinal handling of luminally administered rutin in an isolated preparation of luminally and vascularly perfused rat small intestine. A synthetic perfusate free from blood components was used as vascular medium, with a perfluorocarbon as oxygen carrier. Luminal media consisted of a bicarbonate-buffered sodium chloride solution spiked with rutin (40.5 +/- 1.8 micromol/L). Viability was maintained during the entire perfusion; no differences between rutin and control perfusions for perfusion pressure, lactate-pyruvate ratio, oxygen uptake, and acid-base homeostasis were observed. About 10% of the administered rutin appeared at the vascular side, chiefly as free rutin (5.6%), but some rutin sulfate (2.5%) and glucuronide (2.0%) were also detected. The conjugates were preferentially absorbed to the vascular side, while only traces of the glucuronide (0.2%) were found in the luminal perfusate. Minute amounts of the rutin administered were located in the intestinal tissue (1.1%) in the form of unchanged rutin and its glucuronide and sulfate conjugates. The model used serves as a valuable tool for understanding intestinal handling of the bioactive flavonol glycoside rutin, and the obtained results confirm uptake of rutin in the rat small intestine.

Human milk as a bioindicator for body burden of PCDDs, PCDFs, organochlorine pesticides, and PCBs.

In the State Laboratory of North Rhine-Westphalia for Food, Pharmaceutical and Environmental Chemistry (Chemisches Landesuntersuchungsamt), more than 600 individual human milk samples have been analyzed for polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs), and more than 1400 individual milk samples have been analyzed for organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) since 1984. All samples were collected on a voluntary basis from nursing mothers mostly living in North Rhine Westphalia, a federal state in Germany. The samples analyzed so far show a typical pattern of PCDDs and PCDFs. Out of the 210 possible congeners, only those with 2,3,7,8-chlorine substitution were found. While OCDD normally shows the highest concentration, the levels of the other dioxin congeners decrease with decreasing number of chlorine atoms. A different pattern was found for PCDFs. Within this group 2,3,4,7,8-P5CDF is the most abundant congener, followed by the hexachlorodibenzofurans. The mean level of tetrachlorodibenzodioxin (TCDD) was found to be of 3.2 pg/g on a fat basis and for total PCDDs and PCDFs, calculated as I-TEq (NATO/CMMS), 29.3 pg/g on a fat basis. The investigations of the past 2 years have revealed somewhat lower levels compared to former years. This might be an indication that the efforts undertaken to minimize dioxin emissions and to shut down known sources have already had an effect on the body burden of humans. Although mostly banned for a considerable period of time now, some lipophilic persistent pesticides such as DDT, dieldrin, hexachlorobenzene (HCB), and hexachlorocyclohexanes (HCH) can still be found in human milk.(ABSTRACT TRUNCATED AT 250 WORDS)

Polychlorinated biphenyl levels in the tissues of exposed and nonexposed humans.

Polychlorinated biphenyls (PCBs) are synthetic chemicals, manufactured in volume from about 1929 to the 1970s. Environmental contamination by PCBs has been documented in various substances, including human tissue. PCBs have been measured in human tissue by a variety of analytical methods. PCB levels have been reported as an approximation of total PCB content expressed in terms of a commercial mixture, by identification and quantification of chromatographic peaks, or by qualitative and quantitative characterization of specific congeners. Until recently, the coplanar mono-ortho- and di-ortho substituted PCBs, which are especially toxic and present in significant concentration in humans from industrial countries, had not been measured in human tissues. Examples of various types of commonly used analyses are presented in general population subjects and in persons who experienced special exposure. In this paper, the usefulness of PCB blood determinations following potential exposure is demonstrated, and their application in health studies is illustrated from a number of case studies. Coplanar PCB, mono-ortho-substituted and di-ortho-substituted PCB levels in human blood are presented and compared with polychlorinated dioxin (PCDD) and polychlorinated dibenzofuran (PCDF) levels in the U.S. population. Dioxin toxic equivalents for the two groups of chemicals are calculated and compared. It is found that mono-ortho-substituted and, to a lesser extent, coplanar PCBs, contribute substantially to dioxin toxic equivalents (TEq) in blood from U.S. adults. Because of substantial PCB contribution to dioxin toxic equivalents, total dioxinlike toxicity can only be determined if dioxins, dibenzofurans, and dioxinlike PCBs are measured.(ABSTRACT TRUNCATED AT 400 WORDS)

Chlorinated dioxins and dibenzofurans in human tissue from general populations: a selective review.

During the past decade a considerable amount of data has been generated concerning polychlorinated dibenzodioxin (PCDD) and polychlorinated dibenzofuran (PCDF) levels in humans from many geographical locations. To organize these data in a useful fashion for environmental purposes and for consideration of human toxicity, selected portions of our data are presented in a somewhat atypical fashion, by percentage contribution of individual congeners to total PCDD/Fs in human tissue, and to the total dioxin equivalents (TEq). This is done to better characterize congener contributions from environmental contamination in various geographical regions at this time and health-related levels. To present the findings in a global perspective, data from widely different locations are presented including the United States, Germany, Vietnam, the former Soviet Union, Thailand, Cambodia, China, South Africa, and Guam.