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Background: Previously, we reported an association between higher maternal polychlorinated biphenyl (PCB) concentrations and smaller thymus volume in newborns in a birth cohort residing in eastern Slovakia., Objective: In the present report we address whether thymus volume at later ages is influenced by prenatal and early postnatal PCB exposure., Methods: At the time of delivery, 1,134 mother-infant pairs were enrolled. Maternal and 6- and 16-month infant blood samples were collected and analyzed for 15 PCB congeners. Thymus volume was measured in infants shortly after birth and at ages 6 and 16 months using ultrasonography., Results: Higher maternal PCB concentration was associated with reduced thymus volume at birth [a 0.21 SD reduction in thymus volume for an increase in total maternal PCB concentration from the 10th to the 90th percentile; 95% confidence interval (CI): -0.37, -0.05], whereas maternal PCB concentration was not predictive of 6- and 16-month thymus volume. Six-month infant PCB concentration was associated with a 0.40 SD decrease in 6-month thymus volume (95% CI: -0.76, -0.04). There was also some suggestion that thymus volume at 16 months was positively associated with concurrent infant PCB concentration., Conclusions: The potential adverse effects of in utero PCB exposure on thymic development may extend beyond the neonatal period. Results from this highly exposed cohort provide suggestive evidence that postnatal PCB concentrations may be influential, but a smaller set of 6-month PCB measurements limited statistical power at that time point. Implications regarding impaired immunologic maturation or long-term clinical implications remain to be determined.

Animal data indicate that developmental tetrachlorodibenzo-p-dioxin exposure alters immune function; however, the potential immunotoxicity of dioxin-like and non-dioxin-like polychlorinated biphenyls (PCBs) in the developing infant is an understudied area. The aim of the current study is to examine the association between maternal and early postnatal PCB concentrations in relation to total infant serum immunoglobulin concentrations determined at 6-months-of-age. We selected 384 mother-infant pairs participating in a birth cohort study in Eastern Slovakia. PCB concentrations of several congeners were determined in maternal and cord serum samples and in infant serum samples collected at 6-months-of-age using gas chromatography with electron capture detection. Total immunoglobulin (Ig) G, A, and M concentrations were determined by nephelometry, and IgE concentrations were determined by enzyme-linked immunoassay. Linear regression models with adjustment for potential confounding factors were used to estimate the associations between maternal, cord, and 6-month infant PCB concentrations and total serum immunoglobulins. The median maternal serum concentration of PCB-153 was 140?ng/g lipid, ?10-fold higher than concentrations in childbearing-age women in the United States during the same period. Maternal, cord, or 6-month infant PCB concentrations were not associated with total serum immunoglobulin levels at 6 months, regardless of the timing of PCB exposure, PCB congener, or specific immunoglobulin. In this population, which has high PCB concentrations relative to most populations in the world today, we did not observe any association between maternal and early postnatal PCB concentrations and total immunoglobulin measures of IgG, IgA, IgM, or IgE.

Background: Polychlorinated biphenyls (PCBs) are ubiquitous environmental toxins. Although there is growing evidence to support an association between PCBs and deficits of neurodevelopment, the specific mechanisms are not well understood. The potentially different roles of specific PCB groups defined by chemical structures or hormonal activities e.g., dioxin-like, non-dioxin like, or anti-estrogenic PCBs, remain unclear. Our objective was to examine the association between prenatal exposure to defined subsets of PCBs and neurodevelopment in a cohort of infants in eastern Slovakia enrolled at birth in 2002-2004., Methods: Maternal and cord serum samples were collected at delivery, and analyzed for PCBs using high-resolution gas chromatography. The Bayley Scales of Infant Development -II (BSID) were administered at 16 months of age to over 750 children who also had prenatal PCB measurements., Results: Based on final multivariate-adjusted linear regression model, maternal mono-ortho-substituted PCBs were significantly associated with lower scores on both the psychomotor (PDI) and mental development indices (MDI). Also a significant association between cord mono-ortho-substituted PCBs and reduced PDI was observed, but the association with MDI was marginal (p = 0.05). Anti-estrogenic and di-ortho-substituted PCBs did not show any statistically significant association with cognitive scores, but a suggestive association between di-ortho-substituted PCBs measured in cord serum and poorer PDI was observed., Conclusion: Children with higher prenatal mono-ortho-substituted PCB exposures performed more poorly on the Bayley Scales. Evidence from this and other studies suggests that prenatal dioxin-like PCB exposure, including mono-ortho congeners, may interfere with brain development in utero. Non-dioxin-like di-ortho-substituted PCBs require further investigation.

Background: Extensive experimental data in animals indicate that exposure to polychlorinated biphenyls (PCBs) during pregnancy leads to changes in offspring immune function during the postnatal period. Whether developmental PCB exposure influences immunologic development in humans has received little study., Methods: The study population was 384 mother-infant pairs recruited from two districts of eastern Slovakia for whom prospectively collected maternal, cord, and 6-month infant blood specimens were available. Several PCB congeners were measured in maternal, cord, and 6-month infant sera by high-resolution gas chromatography with electron capture detection. Concentrations of IgG-specific anti-haemophilus influenzae type b, tetanus toxoid, and diphtheria toxoid were assayed in 6-month infant sera using ELISA methods. Multiple linear regression was used to estimate the relation between maternal, cord, and 6-month infant PCB concentrations and the antibody concentrations evaluated at 6-months of age., Results: Overall, there was little evidence of an association between infant antibody concentrations and PCB measures during the pre- and early postnatal period. In addition, our results did not show specificity in terms of associations limited to a particular developmental period (e.g. pre- vs. postnatal), a particular antibody, or a particular PCB congener., Conclusions: At the PCB concentrations measured in this cohort, which are high relative to most human populations today, we did not detect an association between maternal or early postnatal PCB exposure and specific antibody responses at 6-months of age., (Published by Elsevier Inc.)

Experimental evidence from animals indicates that exposure to polychlorinated biphenyls (PCBs) causes deterioration of the outer hair cells (OHCs) of the cochlea. To test this hypothesis in humans, we measured serum PCB concentrations in 574 12-year-old children residing in three districts in the Slovak Republic using high-resolution gas chromatography with microelectron capture detection. As a marker of cochlear status, we measured transient evoked (TE) and distortion product (DP) otoacoustic emissions (OAEs), and assessed the cross-sectional association between serum PCBs and OAEs. Median total PCB concentrations were 352.8, 150.5, and 134.9 ng/g lipid in Michalovce, Svidnik, and Bratislava, respectively. In multivariate regression models where otoacoustic measures were modeled as a function of log (base 10) PCB concentrations with adjustment for gender, age, and site of examination, dioxin-like PCBs, nondioxin-like PCBs and a PCB grouping targeting upregulation of hepatic uridine 5'-diphospho-glucuronosyltransferase were significantly associated with lower TEOAE powers at 1000 and 1500 Hz. At 1500 Hz, we observed a strong association with sum of PCBs and DL-PCBs, in the left ear only. The DPOAEs at 1000 Hz were associated with all four PCB groupings. The results of this study show that PCBs may affect the OHCs of the cochlea, a result consistent with findings from animal studies published to date.

Background: Hydroxylated polychlorinated biphenyls (OH-PCBs), unlike PCBs, are in general readily excreted yet are still detected in humans and animals. Active transport of OH-PCBs across the placenta and hydroxylation of PCBs by the fetus suggest the potential for greater impact on the fetus compared with the parent PCB compounds, but little is known about their health effects, particularly in humans., Objectives: The objective of this study was to evaluate the associations between prenatal OH-PCB exposure and neurodevelopment in children at 16 months of age in eastern Slovakia., Methods: A birth cohort (n = 1,134) was enrolled during 2002-2004. We analyzed six OH-PCB metabolites (4-OH-CB-107, 3-OH-CB-153, 4-OH-CB-146, 3'-OH-CB-138, 4-OH-CB-187, and 4'-OH-CB-172) in a subset of the cohort. The Bayley Scales of Infant Development were administered to the children at the 16-month follow-up visit. We developed multiple linear regression models predicting standardized scores for the Mental Development Index (MDI) and Psychomotor Development Index (PDI) from maternal (n = 147) and cord (n = 80) serum OH-PCB concentrations, adjusting for sex of child, district, HOME (Home Observation for Measurement of the Environment) score, and maternal score on Raven's Progressive Matrices., Results: Cord 4-OH-CB-107 was significantly associated with lower MDI (beta = -2.27; p = 0.01) and PDI (beta = -4.50; p = 0.004). Also, maternal 4-OH-CB-107 was significantly associated with lower MDI (beta = -1.76; p = 0.03) but not PDI. No other OH-PCB metabolites were associated with decreased PDI or MDI., Conclusions: Our findings showed a significant association of 4-OH-CB-107 with decreased MDI, which can possibly be mediated by endocrine disruption, altered neurotransmitter functions, or reduced thyroid hormone concentrations in brain.

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.

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).

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.

Polychlorinated biphenyls (PCBs) were commercially produced between 1959 and 1984 in eastern Slovakia. Improper handling led to a highly contaminated local environment and high levels of PCBs in humans and wildlife in the Michalovce area. The aim of this study was to analyse serum for methylsulfonyl metabolites of PCB (MeSO(2)-PCBs) and DDE (3-MeSO(2)-DDE) in serum samples from pregnant women and in a selected number of paired cord blood samples to assess maternal sulfone levels and patterns, and transplacental transfer of these metabolites. The donating women were from two districts in eastern Slovakia. A liquid-liquid extraction method together with separation of substance groups and further clean-up on silica gel columns were applied prior to analysis by gas chromatography/mass spectrometry. 3-MeSO(2)-DDE was the major methyl sulfone in most of the samples followed by a yet not identified MeSO(2)-hexaCB, 4'-MeSO(2)-CB101, 4'-MeSO(2)-CB87 and 4-MeSO(2)-CB149. The women from the contaminated area had three times higher concentrations of the MeSO(2)-PCBs than women from the reference area. This is the first report on methyl sulfone metabolites of PCB and DDE in human cord serum. It is shown that these metabolites are transported through the placenta. The levels of MeSO(2)-PCBs in the maternal serum were about 1.5 times higher than in the corresponding cord serum on a lipid weight basis. For 3-MeSO(2)-DDE, the levels were about the same in maternal and cord serum. The difference in the maternal:cord ratio, comparing MeSO(2)-PCBs with 3-MeSO(2)-DDE might be due to differences in transport through the placenta caused by their different affinities for lipoproteins and plasma proteins.

The effects of long-term exposure to polychlorinated biphenyls (PCBs) on developmental dental defects of deciduous and permanent teeth in children in eastern Slovakia, where PCBs from a chemical plant manufacturing Delors contaminated the surrounding district were evaluated. Four hundred and thirtytwo children, lifelong residents, aged 8-9 years were examined. Children's caries susceptibility and gingival health was assessed by standard dental indices, and developmental enamel defects by the FDI index. Data from the PCBRISK project data set and questionnaires completed by the parents provided information on exposure and various confounding factors. The proportion of teeth with different types and extensions of developmental enamel defects correlated with serum PCB concentration. The proportion of deciduous teeth affected with enamel defects was significantly higher in higher exposed children (chi(2)=8.35; p=0.03) according to their serum PCB concentration (group 0: <200; group 1: 200-600; group 2: >600 ng PCBs g(-1) serum lipids). The proportion of permanent teeth affected with any enamel defect was significantly higher in higher exposed children (chi2=7.237; p=0.027). Furthermore, the extent of the enamel defects was also greater (chi2=10.714; p=0.005). In multivariate linear regression analysis PCB exposure was significantly related to developmental enamel defects of permanent teeth only. No associations between PCB exposure and caries susceptibility, gingival health or number of teeth were observed. This study demonstrated a dose-response relationship between PCB exposure and developmental enamel defects of permanent teeth in children, the evidence for deciduous teeth was not conclusive.

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.

The levels of 17 toxic polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and 12 non-ortho and mono-ortho polychlorinated biphenyls (PCBs) in 73 foodstuff samples of animal origin collected from shops and small farms in selected districts of Slovak Republic are presented in this paper. The concentrations expressed as WHO-TEQ in analysed samples ranged for PCDDs/PCDFs from 0.25 pg/g fat in pork to 75 pg/g fat in cod liver. The TEQ concentrations of non-ortho PCBs were between 0.007 and 181 pg/g fat and mono-ortho PCBs between 0.0083 and 66.5 pg/g fat. The mean concentrations in freshwater fish and imported species of marine fish were 0.089 pg TEQ/g fresh weight for PCDDs/PCDFs, 0.17 pg TEQ/g fresh weight for non-ortho PCBs and 0.034 pg TEQ/g fresh weight for mono-ortho PCBs. The mean total concentration of PCDDs/PCDFs and dioxin-like PCBs in samples of infant milk formula imported from EU countries was 0.98 pg TEQ/g fat.

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.

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.

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.

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).

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.

Background: Polychlorinated biphenyls (PCBs) are ubiquitous environmental toxins. Although there is growing evidence to support an association between PCBs and deficits of neurodevelopment, the specific mechanisms are not well understood. The potentially different roles of specific PCB groups defined by chemical structures or hormonal activities e.g., dioxin-like, non-dioxin like, or anti-estrogenic PCBs, remain unclear. Our objective was to examine the association between prenatal exposure to defined subsets of PCBs and neurodevelopment in a cohort of infants in eastern Slovakia enrolled at birth in 2002-2004. Methods: Maternal and cord serum samples were collected at delivery, and analyzed for PCBs using highresolution gas chromatography. The Bayley Scales of Infant Development -II (BSID) were administered at 16 months of age to over 750 children who also had prenatal PCB measurements. Results: Based on final multivariate-adjusted linear regression model, maternal mono-ortho-substituted PCBs were significantly associated with lower scores on both the psychomotor (PDI) and mental development indices (MDI). Also a significant association between cord mono-ortho-substituted PCBs and reduced PDI was observed, but the association with MDI was marginal (p = 0.05). Anti-estrogenic and di-ortho-substituted PCBs did not show any statistically significant association with cognitive scores, but a suggestive association between di-ortho-substituted PCBs measured in cord serum and poorer PDI was observed. Conclusion: Children with higher prenatal mono-ortho-substituted PCB exposures performed more poorly on the Bayley Scales. Evidence from this and other studies suggests that prenatal dioxin-like PCB exposure, including mono-ortho congeners, may interfere with brain development in utero. Non-dioxin-like di-ortho-substituted PCBs require further investigation. [ABSTRACT FROM AUTHOR]

Ingestion has been a primary route of PCB exposure for people, especially those not working directly in industrial settings. During 2002–2004, women were recruited at delivery from two districts in eastern Slovakia: Michalovce with high PCB contamination from a chemical manufacturing plant, and Svidnik located 70 km to the northwest, having lower environmental levels of PCBs. Concentrations of 15 PCB congeners were measured in maternal serum using high-resolution gas chromatography with electron capture detection. A food frequency questionnaire was developed and validated at the Research Institute of Nutrition and School of Medicine in Bratislava, Slovakia. The questionnaire was comprised of 88 food items representative of the national dietary habits and designed to ascertain (1) the source of food items as reported by the women (locally produced or purchased from a retail outlet) and (2) quantities consumed of high-fat food categories representative of the national dietary habits. Our primary goal was to identify specific food sources, either locally produced or purchased from retail stores, that might predict serum concentrations of PCBs. We used multiple linear regression to examine the relationship of dietary fats to lipid-adjusted serum PCB levels in 948 adult women (Michalovce N=662, Svidnik N=284) who had recently given birth. We adjusted for residential district, age, body mass index, education and duration of previous lactation. Consumption of fat from locally produced foods was significantly associated with higher levels of lipid-adjusted serum PCB (β=0.06, P=0.007). Fat from foods purchased in retail outlets showed no significant association (β=−0.02, P=0.36). There was no interaction between district and diet in predicting serum PCB levels. Comparing women in Michalovce consuming 20 g of fat per day from local sources with those consuming 1 g of fat per day from local sources, lipid-adjusted serum concentrations were predicted to be higher by 81 ng/g lipid or 14.8% 630 ng/g lipid versus 549 ng/g lipid.Journal of Exposure Science and Environmental Epidemiology (2008) 18, 581–587; doi:10.1038/jes.2008.1; published online 20 February 2008 [ABSTRACT FROM AUTHOR]

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 [β = -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. [ABSTRACT FROM AUTHOR]

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 (ΣPCBs) were 5.73 ng/g wet weight (Michalovce) and 2.82 ng/g wet weight (Svidnik/Stropkov). The median sum of OH-PCBs (ΣOH-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 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 ΣOH-PCBs to the ΣPCBs 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. [ABSTRACT FROM AUTHOR]

Polychlorinated biphenyl (PCB) and polychlorinated dibenzo-p-dioxin and dibenzofuran (PCDD/F) intake via nutrition (nursing, infant milk formula) by infants was evaluated. A cohort of mother-child pairs from an area contaminated with PCB by the Chemko chemical plant formerly producing PCB in eastern Slovakia was examined. Breast milk and blood serum were analysed for PCB and PCDD/F by high resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS). The median daily intake of total toxic equivalent (TEQ) of dioxin-like PCB (dl-PCB) and PCDD/F from breast milk for fully breast-fed children was 72.8 pg·kg-1 body weight per day, assuming 7.6 kg as average body weight of the child. However, daily total intake of TEQ of non-breastfed children during the first 10 month of life was only 0.21 pg·kg-1 body weight per day on average. Dl-PCB-TEQ contributed to the total TEQ in breast milk with a higher proportion (68%) than PCDD/F-TEQ (32%) because of a much higher contamination of breast milk with PCB in general. The median of the sum of non-dioxin-like PCB (ndl-PCB) daily intake assuming 7.6 kg body weight was evaluated as 2 342 ng·kg-1 body weight per day and ranged from 8 ng·kg-1 to 13 124 ng·kg-1 body weight per day. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]