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Consensus holds that pottery technology came to Central Europe from the Northern Balkans with independent pottery traditions existing concurrently in Eastern Europe. An unusual grass-tempered pottery dating back to around 5800 cal BC found in lake sediments at Santovka, Slovakia, predated the earliest known Neolithic pottery in the region (~ 5500 cal BC), suggesting unexplored narratives of pottery introduction. Analyses of the pottery's technology, origin, and grass temper shedding light on ceramic traditions' spread can unveil mobility patterns and community lifestyles. Our findings indicate a non-local provenance, low temperature firing, Festugc sp. grass temper and unique rectangular or cylindrical vessel shapes which align with Eastern European hunter-gatherer practices. Moreover, the pottery style and technology have no analogies in the contemporary Danubian pottery traditions and have more similarities to those of the Eastern traditions. The pottery's raw materials likely originated from distant areas, indicating extensive territorial access for its creators. Our findings imply late Mesolithic hunter-gatherers as the probable artisans and with implications for the site's significance in the late Mesolithic landscape.

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Polychlorinated biphenyls (PCB) were widely used for industrial purposes and consumer products, but because of their toxicity, production was banned by most industrialised countries in the late 1970s. In eastern Slovakia, they were produced until 1985. During 2002-04, a birth cohort of mothers (n = 1057) residing in two Slovak districts was enrolled at delivery, and their specimens and information were collected after birth. Congeners of PCBs were measured in maternal serum by high-resolution gas chromatography with electron capture detection. In this study, we used multiple linear regression to examine the effects of prenatal PCB exposure on birthweight adjusted for gestational age, controlling for inter-pregnancy interval, and maternal smoking, age, education, ethnicity, pre-pregnancy body mass index and height. The association between total maternal serum PCB levels and birthweight was not statistically significant. However, an interaction model indicated that maternal PCB concentrations were associated with lower birthweight in Romani boys. Based on the fitted regression model, the predicted birthweight of Romani boys at the 90th percentile of maternal PCBs (12.8 ng/mL) was 133 g lower than the predicted birthweight at the 10th percentile of maternal PCBs (1.6 ng/mL). This is a similar magnitude of effect to that observed for maternal smoking and birthweight. These results suggest that higher levels of PCBs in maternal blood sera may inhibit growth in boys, particularly in those already affected by social factors related to ethnicity. This study is consistent with previous findings that boys are more susceptible than girls to growth restriction induced by in utero organochlorine exposures, and further indicates that high PCBs may magnify the influence of social disadvantage in this vulnerable group of boys.

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BACKGROUND: Polychlorinated biphenyls (PCBs) are ubiquitous environmental toxicants, for which animal studies demonstrate immunotoxic effects, including thymic atrophy and suppressed immune responses; human investigations of similar end points are sparse. The thymus is essential for the differentiation and maturation of T-cell lymphocytes. OBJECTIVES: The objective of this study was to examine the association between prenatal PCB exposures and estimated thymus volume in infants from eastern Slovakia, a region where PCBs were produced until 1984. METHODS: Mothers were enrolled at delivery, and maternal blood samples were collected for analysis of 15 PCB congeners, p,p'-DDT [1,1,1-trichloro-2,2'-bis(p-chlorophenyl)ethane], and p,p'-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene]. Each mother was interviewed to obtain information on sociodemographic characteristics, past pregnancies, occupational history, medication history, and living environment. Neonatal thymus volume was estimated using ultrasound measurements on the third or fourth day after birth. Thymic index was calculated on 982 newborns from mothers with PCB measurements. We developed a predictive model of the natural log of the thymic index using multiple linear regression with covariates selected from the bivariate analyses. RESULTS: Prenatal PCB exposure was associated with a smaller thymic index at birth [beta= -36 (natural log-transformed; nanograms per gram lipids); p = 0.047]. District of residence and delivery also predicted thymic index. Male sex, later gestational age, larger birth weight z-score, and Roma ethnicity were associated with a larger thymic index, whereas respiratory illness was associated with a lower thymic index. CONCLUSIONS: This study provides the first evidence to date that PCB exposure in neonates is associated with a smaller thymic volume, suggesting possible impaired immunologic development.

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The aim of the present study was to understand the placental transfer of polychlorinated biphenyls (PCBs), specific hydroxylated PCB metabolites (OH-PCBs), and pentachlorophenol (PCP) in blood serum, in a birth cohort from eastern Slovakia. During the period 2002-2004, cord blood specimens were collected in parallel with maternal specimens from women delivering in the two eastern Slovak districts of Michalovce and Svidnik/Stropkov. A total of 92 pairs of mother-cord specimens at delivery were selected for this study. 4-OH-CB107, 3-OH-CB153, 4-OH-CB146, 3'-OH-CB138, 4-OH-CB187, and 4'-OH-CB172 were quantified. The median concentrations of Sigma(17)PCBs, Sigma(6)OH-PCBs, and PCP in cord serum were 0.92, 0.33, and 0.69 ng/g wet wt., respectively and highly correlated with the corresponding maternal serum levels (correlations were R(2)=0.61, 0.78, and 0.82, respectively). The median cord to mother ratios of the Sigma(17)PCBs, Sigma(6)OH-PCBs, and PCP were 0.18, 0.75, and 1.10, respectively. The median ratio of the Sigma(6)OH-PCBs to the Sigma(17) PCBs in the cord serum was 0.38 from wet weight based concentrations, which was about four times higher than the ratio of these compounds in maternal serum (0.09). PCP was more abundant than any PCB or OH-PCB congener measured in cord serum. The higher cord to maternal ratios of OH-PCB metabolites as compared with the parent compounds suggests either a higher placental transfer rate or greater metabolism in the fetus as compared with the maternal compartment. These findings are consistent with their preferential binding to TTR that can cross the placenta. The cord to maternal ratio varies by congener (e.g., 4-OH-CB107=0.58, 4-OH-CB146=0.74, 3'-OH-CB138=1.01).

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In polluted district of Michalovce in East Slovakia (POLL) and two districts with background pollution (BCGR) 2046 adults (834 males and 1212 females aged 20-75 years) were examined. Serum levels of thyrotropin (TSH), free thyroxine (FT4), total triiodothyronine (TT3) and antithyroperoxidase antibodies (TPOab) were estimated by electrochemiluminiscent assay and also these of 15 polychlorinated biphenyl congeners (PCBs), p,p'-DDE, p,p'-DDT, hexachlorobenzene (HCB) and hexachlorocyclohexane were measured by high resolution gas chromatography/mass spectrometry. In addition, also dioxins, furans, coplanar- and mono-ortho-PCBs as well as selected hydroxylated and methylsulphonated PCBs and DDE metabolites were measured by appropriate methods based on gas chromatography/mass spectrometry principle. In POLL significantly higher levels of all organochlorines were found than these in BCGR. When pooled values from both areas were stratified in terms of PCBs level and treated as continuous variables, positive association of PCBs with FT4 and TT3 was found, the latter two being also mutually associated. However, within the category of PCBs level <530 ng/glipid (n=232) the association between PCBs and both the FT4 (p<0.09) and TT3 (p<0.03) was negative and any association of these was not found within the category of PCBs level of 531-1000 ng/g (n=691). In contrast, in the category of 531-2000 ng/g (n=1307) positive association appeared between PCBs and FT4 (p<0.001) as well as TT3 (p<0.05). Highly significant association of PCBs with FT4 (p<0.001) was further found in the categories with PCBs level of 1001-101414 ng/g (n=1307) and 2001-101414 (n=1123), while significant association with TT3 was observed only in the category of 531-2000 ng/g. Such findings suggest possible threshold level in positive effect of PCBs on FT4 and TT3 level which seems to be individual and located somewhere around the PCBs level of 1000 ng/g. However, highly significant negative association of both FT4 and TT3 with TSH was found in each of above indicated PCBs categories. Considerable difference in FT4 and TT3 level between large groups of subjects with the same range of PCBs level was also found suggesting different individual susceptibility to the effects of organochlorines. Among a total of 26 cases from POLL with very low TSH level (<0.5 mU l(-1)) 13 cases showed very high level of PCBs, FT4 and TT3, thus supporting a hypothesis on a novel sporadic form of high PCBs related peripheral subclinical hyperthyroidism possibly resulting from the long-term disruption of equilibrium between bound and free thyroxine in plasma by high PCBs level followed by a striking inhibition of TSH release from the pituitary.

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We examined 2,046 adults (834 males and 1,212 females aged 20-75 years) from polluted district in East Slovakia (POLL) and two neighboring upstream and upwind located districts of background pollution (BCGR). By ultrasound we estimated the thyroid volume (ThV), hypoechogenicity (HYE), nodules and cysts. Serum levels of thyrotropin (TSH), thyroperoxidase antibodies (TPOab) and thyroglobulin were estimated by electrochemiluminiscent assay and these of 15 PCB congeners, p,p'-DDE, p,p'-DDT, hexachlorobenzene (HCB) and hexachlorocyclohexane by high-resolution gas chromatography. In 320 subjects also selected hydroxylated and methylsulfonated PCB metabolites, polychlorinated dibenzo-dioxins (PCDDs), -furans (PCDFs), five dioxin-like coplanar and eight mono-ortho PCB congeners were estimated. Urinary iodine was measured by automatic microplate method. Reciprocal positive association was found between three major POPs (PCBs, DDE and HCB), the levels of these and also PCDDs plus PCDFs in polluted area being considerably higher than in background pollution area. ThV in groups of males and females from POLL with high PCBs level was significantly higher (p<0.001 by t-test) then in age and sex matched groups from BCGR with low PCBs level. In 1,048 males and females aged <60 years with serum PCBs level >1,000 ng g(-1) lipid (median=1,756 ng g(-1)) a significant effect of age on ThV was found (p<0.01 by ANOVA), while in 921 respective subjects with PCBs level <1,000 ng g(-1) (median=661 ng g(-1)) it was not. These findings supported the view on the additional effect of PCBs on ThV other than that of age. Since the urinary iodine in both districts showed optimal range, any interfering effect of unsatisfactory iodine intake on ThV may be excluded. The frequency of autoimmune thyroiditis signs such as HYE, increased serum level of TPOab and TSH resulting in subclinical or overt thyroid hypofunction was positively associated with sex, age and organochlorine levels. The increase of such frequency in males with POPs levels was much more abrupt than that in females. No considerable differences in the frequency of thyroid nodules as related to PCBs level were found.

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OBJECTIVE: Our aim in the present study was to characterize and quantify the levels of polychlorinated biphenyls (PCBs) and specific polychlorobiphenylol (OH-PCB) metabolites in maternal sera from women delivering in eastern Slovakia. DESIGN: During 2002-2004, blood samples were collected from women delivering in two Slovak locations: Michalovce district, where PCBs were formerly manufactured, and Svidnik and Stropkov districts, about 70 km north. PARTICIPANTS: A total of 762 and 341 pregnant women were sampled from Michalovce and Svidnik/Stropkov, respectively, and OH-PCBs were measured in 131 and 31. EVALUATION/MEASUREMENTS: We analyzed PCBs using gas chromatography (GC)/electron capture detection. OH-PCBs and pentachlorophenol (PCP) were determined as methyl derivatives using GC-electron capture negative ionization/mass spectrometry. We characterized distributions in the full cohort using inverse sampling weights. RESULTS: The concentrations of both PCBs and OH-PCB metabolites of Michalovce mothers were about two times higher than those of the Svidnik/Stropkov mothers (p < 0.001). The median weighted maternal serum levels of the sum of PCBs (sigmaPCBs) were 5.73 ng/g wet weight (Michalovce) and 2.82 ng/g wet weight (Svidnik/Stropkov). The median sum of OH-PCBs (ZOH-PCBs) was 0.55 ng/g wet weight in Michalovce mothers and 0.32 ng/g wet weight in Svidnik/Stropkov mothers. 4-OH-2,2',3,4',5,5',6-Heptachlorobiphenyl (4-OH-CB187) was a primary metabolite, followed by 4-OH-2,2',3,4',5,5'-hexachlorobiphenyl (4-OH-CB146). Only four PCB congeners-CBs 153, 138, 180, and 170--had higher concentrations than 4-OH-CB187 and 4-OH-CB146 (p < 0.001). The median ratio of the sigmaOH-PCBs to the sigmaPCBs was 0.10. CONCLUSIONS: Mothers residing in eastern Slovakia are still highly exposed to PCBs, and their body burdens of these pollutants and OH-PCB metabolites may pose a risk for adverse effects on health for themselves and their children.

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In a certain area of Michalovce district in East Slovakia, heavy industrial pollution by polychlorinated biphenyls (PCBs) developed in 1955-1984 and very high PCB levels in environmental and human samples are still persisting. Recently, a total of 2045 adults from this and the surrounding background pollution area have been examined using questionnaire data, thyroid volume by ultrasound (ThV), urinary iodine and serum levels of 15 PCB congeners, hexachlorobenzene (HCB), 2,2'-2-bis(4-chlorobiphenyl)-1,1-dichloroethylene (DDE), 2,2'-bis(4-chlorophenyl)-1,1,1-trichloroethane (DDT), alpha-, beta- and gamma-hexachlorocyclohexane (HCH), thyrotropin (TSH), free thyroxine (FT4), anti-thyroperoxidase antibodies (TPOab) and fasting glucose. As based on our previous findings of strikingly high level of PCBs in fish from high pollution area (e.g. mean level of 375430 ng/g lipid) and considerably lower, but still relatively high level in background pollution area (e.g. mean PCB level of 5150 ng/g), the information on the frequency of fish meals and approximate annual consumption of fish from local waters was obtained by questionnaires. The association of contaminated fish consumption with very high blood levels of PCBs, DDE and HCB and increased ThV as well as with increased frequency of positive TPOab, high values of FT4 and impaired fasting glucose (IFG) was found. These associations were also confirmed in 16 marital pairs from high pollution area with very high PCB level in both members associated with high fish consumption. It was concluded that, due to persistent heavy pollution of waters, soil and food chain namely by PCBs, but also by pesticides (e.g. DDE and HCB) resulting from their previous extensive use in agriculture, the fish from local waters still remains the most important source of these toxic pollutants which results in considerable adverse health effects.

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Human breast milk represents the best choice for the nutrition of infants. It is often used for monitoring human exposures to environmental chemicals. Uniquely suited to meet human biological needs, breast milk composition, especially fat content, changes significantly with time from delivery. With the aim to compare the concentration of organochlorine compounds (OCs) in colostrum versus mature milk, we obtained samples of fourth-fifth day postpartum milk (colostrum) and day-14 postpartum milk (mature milk) from 12 women enrolled in the project "Early Childhood Development and PCB Exposure in Slovakia". The concentrations of selected organochlorine pesticides and congeners of polychlorinated biphenyls (PCBs) were measured using gas chromatography with electron capture detection and reported on lipid adjusted basis. No significant differences were found between organochlorine levels in colostrum and those in mature milk samples. A very close correlation was found between the concentrations of organochlorine compounds in colostrum and mature milk (Spearman correlation coefficient r=0.94-0.98 for PCBs, and r=0.85-0.99 for organochlorine pesticides, p<0.001 for all compounds). The present study concludes that the use of colostrum samples provides a close estimate of the child's exposure to OCs in the early neonatal period and demonstrates that, despite the lower fat content, colostrum specimens are adequate to conduct OC analyses.

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The over-riding aim of the present investigation was to obtain information concerning exposure that can be used as a basis for studies on the health of individuals residing in the Michalovce area of eastern Slovakia which is heavily contaminated by polychlorinated biphenyls (PCBs). Accordingly, this work focused on determination of serum concentrations of hydroxylated (OH-PCBs) and methylsulfonyl-substituted (MeSO2-PCBs) metabolites of PCBs. One hundred and twenty-two men and women, 20-59 years of age, living in the contaminated area and 175 from the control Stropkov/Svidnik district were selected randomly from 2047 sampled individuals. Following a specially designed cleanup, the levels of various congeners of OH-PCBs and MeSO2-PCBs in their serum were quantitated by gas chromatography and mass spectrometry, with comparison to authentic reference standards. The median concentrations of PCB congeners and their OH-PCB and MeSO2-PCB metabolites were 2-3-fold higher in residents of Michalovce than in the control region. The levels of certain OH-PCB metabolites were in the same high range as those of individual PCB congeners, whereas the MeSO2-PCB levels were significantly lower. The PCB and their metabolites were present at slightly higher concentrations in men than in women, and the serum levels of PCBs and MeSO2-PCBs increased with increasing age. Thus, the environmental contamination resulting from previous industrial production of PCBs has led to elevated concentrations of PCBs and their metabolites in the serum of individuals living in the Michalovce area.

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We measured organochlorine concentrations of 15 polychlorinated biphenyl congeners and six organochlorine pesticides (PCB28, 52, 101, 123(+149), 118, 114, 153, 105, 138(+163), 167, 156(+171), 157, 180, 170, 189, alpha-, beta-, gamma-HCH, HCB, p,p'-DDT and p,p'-DDE) in 2047 subjects from contaminated and background areas of eastern Slovakia. Data were collected in 2001 and analyzed by high-resolution gas chromatography with electron capture detection in 2002-2003. Elevated levels persist in subjects from Michalovce district, site of former production facility, after almost 20-years since the end of the PCB manufacturing. Sum of 15 PCB congeners was 3105 ng/g of lipid in the Michalovce district versus 871 ng/g of lipid for subjects from the background districts of Svidnik and Stropkov. Relatively high concentration in children from the Michalovce district, sum PCB = 766 ng/g of lipid versus 372 ng/g of lipid in children from background area suggest ongoing exposure from environmental reservoirs and contaminated food. Consistent differences between genders in both contaminated and background areas are reported here. Levels in males are about 20% higher in both districts. Levels of organochlorine pesticides, particularly of DDT metabolite DDE and hexachlorobenzene are also elevated in the Michalovce district, reflecting intensive use of pesticides in agriculture in the past. About 30% decrease in serum organochlorine levels was observed in comparison with our earlier samples collected in 1998. These results suggest that contamination with PCBs still remains a source of relatively high environmental exposure for subjects in the Michalovce district.

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In the present study, non-ortho, mono-ortho and other ortho-substituted PCB congeners were analysed in individual blood serum samples taken from healthy adults (196 males and 119 females) in the polluted area of the Michalovce district and in the background area of the Stropkov/Svidnik districts in Eastern Slovakia by high resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS). The samples from general population living in villages and towns of two regions were taken between August 2001 and February 2002 within the project of the EC's 5th Framework Programme (PCBRISK, ). The medians of dioxin-like PCBs (dl-PCBs)--expressed as TEQs on lipid basis--of all males (24.7 pg g(-1) lipid) and females (21.4 pg g(-1) lipid) were comparable, but there was a significant difference between both of the areas studied. In the district of Michalovce, the medians of males (47.3 pg g(-1) lipid) and females (41.1 pg g(-1) lipid) were 2.3 times higher than in the area of the Stropkov/Svidnik districts. The medians of total non-dioxin-like PCB concentration were 1,835 and 1,033 ng g(-1) lipid in males and females, respectively. The data show a trend toward higher concentrations of both dl- and non-dioxin-like PCBs in the older age groups. The substantial increase was observed for the 60+ age group. PCB-126 was the most abundant non-ortho congener. PCBs-118 and 156 were the predominant mono-ortho congeners. They were quantitated in all samples analysed. Congeners 153, 138(+163), 180 and 170(+190) were the main contributors to total non-dioxin-like PCB concentrations. Mean mutual ratio HexaCBs:HeptaCBs:OctaCBs in the non-dioxin-like group was 37:50:1. The results of this study represent the overall information about the congener distribution of dioxin-like and non-dioxin-like PCBs in human serum blood of adult Slovaks.

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Polychlorinated biphenyls (PCBs) are thought to cause numerous adverse health effects, but their impact on estrogen signaling is still not fully understood. In the present study, we used the ER-CALUX bioassay to determine estrogenic/antiestrogenic activities of the prevalent PCB congeners and PCB mixtures isolated from human male serum. The samples were collected from residents of an area with an extensive environmental contamination from a former PCB production site as well as from a neighboring background region in eastern Slovakia. We found that the lower-chlorinated PCBs were estrogenic, whereas the prevalent higher-chlorinated PCB congeners 138, 153, 170, 180, 187, 194, 199, and 203, as well as major PCB metabolites, behaved as antiestrogens. Coplanar PCBs had no direct effect on estrogen receptor (ER) activation in this in vitro model. In human male serum samples, high levels of PCBs were associated with a decreased ER-mediated activity and an increased dioxin-like activity, as determined by the DR-CALUX assay. 17beta-Estradiol (E2) was responsible for a major part of estrogenic activity identified in total serum extracts. Significant negative correlations were found between dioxin-like activity, as well as mRNA levels of cytochromes P450 1A1 and 1B1 in lymphocytes, and total estrogenic activity. For sample fractions containing only persistent organic pollutants (POPs), the increased frequency of antiestrogenic samples was associated with a higher sum of PCBs. This suggests that the prevalent non-dioxin-like PCBs were responsible for the weak antiestrogenic activity of some POPs fractions. Our data also suggest that it might be important to pay attention to direct effects of PCBs on steroid hormone levels in heavily exposed subjects.

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Risks of carcinogenic and non-carcinogenic effects from asbestos continue owing to the persistence of the fibres in building materials and other products. For this reason, epidemiological and mechanistic research on the toxic effects of asbestos and mineral fibres is still needed. The present molecular epidemiological study was conducted in a former asbestos cement plant in Slovakia. Altogether 82 subjects were investigated, 61 exposed subjects (24 smokers and 37 non-smokers), and 21 factory controls (8 smokers and 13 non-smokers). Workers were exposed to asbestos for between 5 and 40 years. Though the exposure to asbestos during past 40 years was relatively high, at the time of sampling the concentrations of asbestos in the production hall exceeded the Slovak occupational limit (0.001 fibre/cm3) by a factor of only 3-5. The office area levels were below this limit. Biomarkers of exposure, effect and individual susceptibility were measured, including DNA damage (strand breaks [SBs], base oxidation and alkylation, using the comet assay); cytogenetic parameters; and individual DNA repair capacity (incision at 8-oxoguanine measured using a modified comet assay). Oxidised pyrimidines were significantly higher in exposed men compared with non-exposed (P = 0.04). There was also a positive association between SBs (P = 0.04) and age, and alkylation damage to DNA (P = 0.04) and age. Moreover, oxidised pyrimidines (P = 0.01) and alkylated bases (P = 0.001) strongly correlated with years of occupational exposure. Micronucleus frequency did not differ between exposed and control subjects. Repair capacity overall did not show any effect of exposure, though female controls had higher incision rates than did female exposed subjects. However, exposed asbestos workers had significantly higher numbers of chromosomal aberrations (P = 0.01) compared with control group. This finding is consistent with the known association of chromosome aberrations with cancer-risk.

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In a population-based cross-sectional study, we compared serum levels of 15 polychlorinated biphenyl (PCB) congeners and three organochlorine pesticides in residents of two districts in eastern Slovakia, one with extensive environmental contamination from a former PCB production site (Michalovce) and the other matched on geography but with low (background) levels (Svidnik). The age-adjusted geometric means for sum of 15 measured PCB congeners were statistically significantly higher in subjects from the Michalovce district for both sexes: 3327.6 versus 1331.4 ng/g of lipid in males, 2751.8 versus 992.2 ng/g of lipid in females. Levels of DDE and DDT were also significantly higher, although the absolute differences were less pronounced. There was no substantial difference in HCB levels between the districts. We also conducted an ecologic study to compare cancer incidence occurring in these same two districts from 1985 through 1994. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals for each district using indirect standardization and rates from eastern Slovakia. Among males from Michalovce (exposed), but not Svidnik (unexposed), there was an excess of cancer of the tongue (SIR=1.46; 1.06-1.96), stomach (SIR=1.15; 1.00-1.32), lung (SIR=1.14; 1.04-1.24), testis (SIR=1.40; 0.97-1.97), and kidney (SIR=1.23; 0.98-1.52), and lower than expected incidence of prostate cancer (SIR=0.83; 0.69-0.97); in contrast, there was an excess of peritoneal (SIR=3.05; 1.11-6.63) and laryngeal cancer (SIR=1.43; 0.99-1.98) in Svidnik not observed Michalovce. Among females from Michalovce, but not Svidnik, there was an excess of cancer of the lip (SIR=2.54; 1.53-3.96), stomach (SIR=1.22; 1.02-1.44), and lung (SIR=1.17; 0.94-1.45); in contrast, there was an excess of kidney (SIR=1.61; 1.03-2.40) and thyroid (SIR=1.97; 1.12-3.20) cancer in Svidnik not observed in Michalovce. Taken together, these results raise the possibility that high environmental exposure to organochlorines in the Michalovce district may be associated with higher rates of certain cancers, particularly stomach and lung cancer.

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This case-control study was designed to investigate association between polychlorinated biphenyls (PCBs) and risk of breast cancer in an area of high environmental exposure in the Michalovce district of eastern Slovakia. Incident breast cancer cases from the Michalovce district diagnosed between May 1997 and May 1999 were recruited through the Oncology Department of the District Hospital. A total of 15 individual PCB congeners, 2,2'-bis(4-chlorophenyl)-1,1-dichloroethylene (DDE), 2,2-bis(4-chlorophenyl)-1,1,1-trichloroethane (DDT), and hexachlorobenzene (HCB) were measured in the serum of 24 breast cancer patients and 88 population controls in 1998-1999. The median levels of total PCBs were similar in cases (2586 ng/g of lipid) and controls (2682 ng/g of lipid). Higher serum levels (highest vs. lowest tertile) of total PCBs (odds ratio (OR)=0.42, 95% CI 0.10-1.82, p-for trend=0.31), group 1 congeners (OR=0.37, 95% CI 0.10-1.43, P-for trend=0.02), group 2 congeners (OR=0.32, 95% CI 0.07-1.56, P-for trend=0.60), and group 3 congeners (OR=0.49, 95% CI 0.12-2.04, P-for trend=0.51) were inversely associated with risk of breast cancer. Higher serum levels of DDE (OR=3.04, 95% CI 0.65-14.3, P-for trend=0.10) were positively associated with risk of breast cancer, while there was no association for DDT (OR=1.19, 95% CI 0.27-5.23, P-for trend=0.68), and an inverse association for HCB (OR=0.45, 95% CI 0.06-3.19, P-for trend=0.67). While generally not statistically significant, PCB and HCB levels were inversely associated with risk of breast cancer in this highly exposed population. DDE, but not DDT, was positively associated with risk.

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The purpose of this work was to study the effects of high environmental exposure to polychlorinated biphenyls (PCBs) and other organochlorines on the thyroid. Thyroid volume, hypoechogenicity and nodules (by ultrasound), presence of antithyroid peroxidase (anti-TPO) antibodies, and abnormal thyroid-stimulating hormone (TSH) levels in serum (by radioimmunoassay) were examined in 101 adults from the PCB-polluted area in 360 controls. Serum levels of PCBs, hexachlorobenzene, gamma-hexachlorocyclohexane (HCH), p,p'-DDT(1,1,1-trichloro-2,2'-bis(p-chlorophenyl)ethane), and p,p'-DDE(1,1-dichloro-2,2'-bis(p-chlorophenyl)ethene) were measured by high-resolution gas chromatography. Very high levels of PCBs were found in the polluted area (7300 +/- 871 ng/g lipids) compared with controls (2045 +/- 147 ng/g). Positive correlations (P < 0.001) were found between the levels of all organochlorines and their total except for hexachlorocyclohexane (HCH). In the polluted area, the highest thyroid volumes (18.7 +/- 2.32 mL; mean +/- SE) were clustered among 23 subjects (17 males and six females) with PCB levels above 10,000 ng/g (range 10,000-58,667 ng/g). In the remaining 438 subjects the thyroid volume was 14.2 +/- 0.29 mL. These data suggest that there might be a threshold serum PCB level of approximately 10,000 ng/g that may influence the thyroid volume. A two-way ANOVA showed that all thyroid volumes in the polluted area were significantly higher (P < 0.001) than in the control area. In males from the polluted area, the frequencies of thyroid hypoechogenicity, thyroid nodules, positive anti-TPO, and abnormal TSH level were higher than in males from the control area, whereas such differences were not observed in females. Increased thyroid volume and indicators of potential thyroid dysfunction were associated with long-term environmental exposure to PCBs. These effects on the thyroid were confined to subjects with PCB levels above 10,000 ng/g of lipid (thyroid volume) and to males from the polluted area (thyroid hypoechogenicity, thyroid nodules, positive anti-TPO, and abnormal TSH).

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An increased prevalence of thyroid antibodies was seen in employees of a factory that formerly produced polychlorinated biphenyls (PCBs). In this study, the authors expand the evaluation of possible long-term PCB effects by comparing the prevalence of glutamic acid decarboxylase (anti-GAD) antibodies with the development of diabetes mellitus. The sera of 240 factory employees and 704 control subjects were analyzed. Anti-GAD antibody values exceeded 1.20 U/ml in all employees (40.4%), was 4 times higher (p < .001) than in all controls (10.5%), and were 5 times higher in employees aged 51-60 yr (53.2%) than in age-matched controls (10.5%) (p < .001). Although the prevalence of diabetes could not be determined from this retrospective study, this is the first report of a possible relationship between xenobiotics and the prevalence of anti-GAD antibodies, and it supports the concept of an immunomodulatory effect of PCBs. However, such antibodies may be present decades before the development of clinical diabetes, and not all anti-GAD antibody-positive individuals become diabetic. Presently, it is unknown whether there is an increased prevalence of diabetes among the former factory employees.

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