Gene expression signatures in PCB-exposed Slovak children in relation to their environmental exposures and socio-physical characteristics.

Our previous gene expression studies in a PCB-exposed cohort of young children in Slovakia revealed that early-life exposures to PCBs and other organochlorine compounds were associated with significant alterations across several pathogenetic pathways. The present study was undertaken to further explore the high-throughput qRT-PCR-based gene expression effects by using TaqMan low-density array (TLDA) for selected genes in a sample of 55 children from the cohort. We analyzed the transcriptional changes of 11 genes in relation to PCB and organochlorine pesticide exposure levels (including DDT, DDE, HCH, and HCB), and to BMI and ethnicity in this cohort. The results indicated an overall downregulation of expression of these genes. Maximum downregulation (in fold change) was observed in the ENTPD3 gene, and the minimum level of downregulation was in CYP2D6. As per our multinomial regression model study, downregulation of LEPR gene was significantly directly correlated with all the exposure variables. Downregulation of APC, ARNT, CYP2D6, LEPR, LRP12, and MYC genes was directly correlated with BMI (kg/m2) of the individuals. Gender-specific differences in gene expression were observed in CYP2D6 (p-value 0.0001) and LEPR (p-value 0.028), while downregulation of CYP2D6 (p-value 0.01), LEPR (p-value 0.02), LRP12 (p-value 0.04), and MYC (p-value 0.02) genes was consistently observed in Roma children compared to Caucasians. The investigation of such health disparities must be emphasized in future research, together with interventions to reduce the health consequences of PCB exposures. In this context, we emphasize the importance of biomarker-based approaches to future research on genetic susceptibility to the effects of these compounds.

Application of a pharmacokinetic model in characterizing sources of polychlorinated biphenyl exposure and determining threshold daily intakes for adverse health effects in infants and toddlers.

Characterization of PCB exposure sources for vulnerable population groups is essential to minimize the health effects of PCB exposure. At the same time, it is important to consolidate the knowledge on threshold intakes of PCBs for infants and toddlers to prevent health effects. We estimated total PCB concentrations from birth to 2 years of age in children from Slovak and Czech populations, which continue to have high PCB concentrations in breast milk. Using a pharmacokinetic (PK) model, we characterized dominant PCB exposure sources and estimated new threshold estimated daily intakes (TEDI) (above which adverse effects cannot be excluded) for postnatal PCB exposure in infants and toddlers. In the PK model, concentrations of seven indicator PCBs in breast milk and cord blood samples from 291 mother-child pairs from the Slovak birth cohort, and 396 breast milk samples from Czech mothers we used, together with their physiological characteristics and PCB concentrations from other exposure sources (food, dust, air). The estimated total PCB concentrations in children's blood at different ages were compared with threshold PCB concentrations of 500, 700 and 1000 ng·glipid-1 in serum proposed by the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) and the German Environment Agency (UBA), above which possible adverse health effects may be expected. We estimated that up to 20.6% of Slovak children and up to 45.7% of Czech children at two years of age exceeded the threshold value of 700 ng·glipid-1 in blood. Mean TEDIs leading to values of 500 ng·glipid-1 in blood for children up to two years ranged between 110 and 220 ng·kg-1·bw·day-1, varying according to breastfeeding duration. Breast milk and prenatal exposure contributed to 71%-85% of PCBs exposure at two years of age. In contrast, the contributions of PCBs from dust and indoor air were negligible.

Pre- and postnatal polychlorinated biphenyl exposure and cognitive and behavioral development at age 45 Months in a cohort of Slovak children.

Evidence of associations of pre- and postnatal exposure to polychlorinated biphenyls (PCBs) with cognitive development beyond early childhood is inconsistent. A previous report from this cohort observed adverse associations between early life PCB exposures and infant Bayley scores at age 16 months. The present study examines pre- and postnatal PCB exposures in relation to both behavior and cognitive development at age 45 months. Participants were 472 mother-child pairs residing in an area of eastern Slovakia characterized by environmental contamination with PCBs, which resulted in elevated blood serum concentrations. PCB-153 and PCB-118 concentrations were measured in maternal and in infant 6-, 16-, and 45-month serum samples. At age 45 months, children were administered five subtests of the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III), and mothers completed the Child Behavior Checklist (CBCL). Negative binomial and multiple linear regressions were used to estimate PCB-CBCL and PCB-WPPSI-III subtest score associations, respectively. Pre- and postnatal levels of PCB-153 and PCB-118 were not associated with cognitive performance on the WPPSI-III in this cohort. There was some suggestion that higher postnatal PCB concentrations were associated with more sleep problems and feelings of depression and anxiousness.

PBDE serum concentration and preschool maturity of children from Slovakia.

Polybrominated diphenylethers (PBDEs) are persistent organic pollutants (POPs), they are considered endocrine disruptors and can bioaccumulate in nature, and in living tissue. Human exposure to and the presence of PBDEs in human samples is of concern due to their potential health risks. Young children are one of the most vulnerable populations to PBDE's potential health effects. Ninety-one serum samples of 6-year-old children, residing in a contaminated location, due to former production of polychlorinated biphenyls (PCBs), were analysed to examine children's exposure to PBDEs in Slovakia. Median serum concentrations found for individual PBDE congeners BDE-28+33, -47, -99, -100, -153, -154 and -183 were 0.015, 0.184, 0.079, 0.046, 0.176, 0.014, and 0.097 ng g-1 lipid weight, respectively. Children's preschool maturity was measured using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) test. In multivariate analyses BDE-153 serum concentrations were significantly inversely associated with WPPSI-III composite score (p = 0.011, ß = -23.6), while adjusting for PCB-153 and sex. Significant negative associations were observed for BDE-153 serum concentrations (p = 0.002, ß = -29.8) and WPPSI-III composite score, after controlling for PCB-118 and sex. Negative associations were also observed for BDE-47, BDE-100 and BDE-153, with different individual WPPSI subtest scores, after adjustment with PCB-153 and/or PCB-118 and sex. Serum concentrations of PCB-153 and PCB-118 were not statistically significantly associated with WPPSI-III composite score and individual subtest scores. These findings demonstrate adverse effects of PBDE serum exposure on preschool maturity of children, and PBDEs potentially negative impact on child neuropsychological development.

The spatial distribution of congener-specific human PCB concentrations in a PCB-polluted region.

Serum PCB congener concentrations were measured in 602 adults living near a PCB pollution source in eastern Slovakia. We created isoconcentration maps for 21 PCB congeners by geocoding each participant's place of residence and kriging. Concentrations of PCB congeners were inversely associated with the distance of the participants' residence from the source of pollution. Congener-specific risk factors were derived, particularly for PCBs 52 and 153. We observed that the spatial distribution of serum concentrations was influenced by micro-climatic parameters and physicochemical properties of the congeners. PCB congener profiles strongly correlated with that of the PCB commercial product Delor 106, which was manufactured in the region. The isoconcentration maps indicate that the zones with the highest predicted congener concentration have a mean area of approximately 235.75±188.56km2 and the mean enrichment of concentration of congeners in serum in these zones is about 5.12±1.36. We estimate that depending on congener approximately 23,457±18,762 individuals with PCB concentrations exceeding health-based guidance values live in these zones.

PCB exposure and cochlear function at age 6 years.

Epidemiological studies have documented adverse associations between exposure to polychlorinated biphenyls (PCBs) and otological outcomes. Previously, we documented decreased distortion product otoacoustic emission (DPOAE) levels in children exposed to PCBs, up to the age of 45 months, amongst a cohort of children in eastern Slovakia. The objective of the present study is to evaluate cochlear dysfunction at 72 months of age in 214 children from this same cohort and to compare the otoacoustic test sensitivity to that of pure tone audiometry (PTA). The association between DPOAE, PTA, and PCBs was estimated by means of multivariate ANOVA (MANOVA) and linear regression models. ROC curves were computed to estimate the DPOAE-test power in children. The DPOAE level at 72 months was related to PCB-153 serum levels. The DPOAE Input/Output function test at mid-frequency (2kHz) has shown instead nonmonotonic dependence on PCB exposure, for the left ears of children, over the whole growth curve. No significant association was found between PTA hearing levels and PCB-153 concentration. High diagnostic power of the DPOAE-test was found in children, similar to that found by the same authors in adults. In conclusions the DPOAE-PCB correlation obtained at 72 months is similar to that at 45 months suggesting a permanent and stable ototoxic effect of the PCB exposure. The lack of statistical significance of the PCB-PTA correlation suggests that DPOAEs are sensitive biomarkers of cochlear damage.

Demographic, Reproductive, and Dietary Determinants of Perfluorooctane Sulfonic (PFOS) and Perfluorooctanoic Acid (PFOA) Concentrations in Human Colostrum.

To determine demographic, reproductive, and maternal dietary factors that predict perfluoroalkyl substance (PFAS) concentrations in breast milk, we measured perfluorooctane sulfonic (PFOS) and perfluorooctanoic acid (PFOA) concentrations, using liquid chromatography-mass spectrometry, in 184 colostrum samples collected from women participating in a cohort study in Eastern Slovakia between 2002 and 2004. During their hospital delivery stay, mothers completed a food frequency questionnaire, and demographic and reproductive data were also collected. PFOS and PFOA predictors were identified by optimizing multiple linear regression models using Akaike's information criterion (AIC). The geometric mean concentration in colostrum was 35.3 pg/mL for PFOS and 32.8 pg/mL for PFOA. In multivariable models, parous women had 40% lower PFOS (95% CI: -56 to -17%) and 40% lower PFOA (95% CI: -54 to -23%) concentrations compared with nulliparous women. Moreover, fresh/frozen fish consumption, longer birth intervals, and Slovak ethnicity were associated with higher PFOS and PFOA concentrations in colostrum. These results will help guide the design of future epidemiologic studies examining milk PFAS concentrations in relation to health end points in children.

A Birth Cohort Study of Maternal and Infant Serum PCB-153 and DDE Concentrations and Responses to Infant Tuberculosis Vaccination.

BACKGROUND: Reasons for the highly variable and often poor protection conferred by the Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine are multifaceted and poorly understood. OBJECTIVES: We aimed to determine whether early-life exposure to PCBs (polychlorinated biphenyls) and DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] reduces 6-month infant BCG vaccine response. METHODS: Data came from families participating in a prospective birth cohort in eastern Slovakia. At birth, maternal and cord blood were collected for chemical analyses, and infants were immunized with BCG. Blood was collected from infants for chemical analyses and to determine 6-month BCG-specific immunoglobulin (Ig) G and IgA levels. Multivariable linear regression models were fit to examine chemical-BCG associations among approximately 500 mother-infant pairs, with adjustment for confounders. RESULTS: The median 6-month infant concentration of the prevalent congener PCB-153 was 113 ng/g lipid [interquartile range (IQR): 37-248], and 388 ng/g lipid (IQR: 115-847) for DDE. Higher 6-month infant concentrations of PCB-153 and DDE were strongly associated with lower 6-month BCG-specific antibody levels. For instance, BCG-specific IgG levels were 37% lower for infants with PCB-153 concentrations at the 75th percentile compared to the 25th percentile (95% CI: -42, -32; p < 0.001). Results were similar in magnitude and precision for DDE. There was also evidence of PCB-DDE additivity, where exposure to both compounds reduced anti-BCG levels more than exposure to either compound alone. CONCLUSIONS: The associations observed in this study indicate that environmental exposures may be overlooked contributors to poorer responses to BCG vaccine. The overall association between these exposures and tuberculosis incidence is unknown. CITATION: Jusko TA, De Roos AJ, Lee SY, Thevenet-Morrison K, Schwartz SM, Verner MA, Palkovicova Murinova L, Drobná B, Kocan A, Fabisiková A, Conka K, Trnovec T, Hertz-Picciotto I, Lawrence BP. 2016. A birth cohort study of maternal and infant serum PCB-153 and DDE concentrations and responses to infant tuberculosis vaccination. Environ Health Perspect 124:813-821; http://dx.doi.org/10.1289/ehp.1510101.

The spatial distribution of human exposure to PCBs around a former production site in Slovakia.

We evaluated concentrations of 15 PCB congeners in blood serum of 2047 adults, 431 8-9-year old children and 1134 mother-child pairs born in 2001-2003. These subjects were long-standing residents living up to 70 km (to the north) and up to 50 km (to the south) of the former Chemko Strázske PCB production facility in the Michalovce district of Slovakia. We plotted serum concentration against distance from the plant both with and without consideration of the direction of their homes from the site. The decrease in exposure with distance could be described by an exponential function which was dependent on direction and climatic parameters. By kriging we created maps depicting predicted isoconcentration contours for sex- and age-adjusted serum concentration of ∑PCBs for the same group of children, adults and mothers. The principle of our risk analysis was to relate serum concentration data, reflecting PCB body burden, using the critical concentrations established by the French Agency for Food, Environmental and Occupational Health & Safety (ANSES 2010) as thresholds below which the probability of effects on health is regarded as negligible. We conclude that 10 years ago, around 200,000 residents were at risk in this densely populated area. Exposure has since decreased but the mechanism for this has not yet been studied.

Ratio of cord to maternal serum PCB concentrations in relation to their congener-specific physicochemical properties.

The aim was to characterize placental transfer of some congeners of polychlorinated biphenyls (PCBs) and to relate human in utero exposure to these pollutants to their physicochemical properties. We included into the study 1134 births during the period 2002-2003 from two highly PCB contaminated districts in eastern Slovakia. Concentrations of 15 PCB congeners (IUPAC No. 28, 52, 101, 123(+149), 118, 114, 153, 105, 138(+163), 167, 156(+171), 157, 180, 170, and 189) in umbilical cord (C) and maternal serum (M) were determined. The C/M ratios were significantly related, either positively or inversely depending on parameter, to the logarithm of partition coefficient octanol-water (KOW), to fusion enthalpy at the melting point, molecular weight, water solubility, total surface area of the molecule, solvent accessible surface area, melting point, molar volume, and molecular electronegativity distance vector. We found an inverse association between logKOW and lipid adjusted logC/M (const=1.078, b1=-0.179, p<0.001, R(2)=0.039). Parameters evaluated were interrelated except fusion enthalpy at the melting point and electron affinity vs. solubility. We discuss the possible role of cholesterol as a transplacental transporter of PCBs.

Duration of breastfeeding and serum PCB 153 concentrations in children.

Polychlorinated biphenyls (PCBs) are toxic, persistent, and bioaccumulative chemicals which, because of their lipophilic properties, are abundant in human breast milk. Breastfed infants are therefore at risk of being exposed to considerable amounts of PCBs. The commonly used exposure estimations, based solely on breast milk PCB levels and duration of breastfeeding, may lead to exposure misclassification. To improve assessments of exposure to PCBs, we determined PCB 153 serum concentration, as a model substance for PCBs, at the critical time of weaning for each child in 305 breastfed infants from 5 single time point concentration measurements spread over 7 years and data on duration of breastfeeding, using an earlier developed model of the system type. We approximated the dependence of PCB 153 serum concentration, Ctbf, adjusted to cord serum concentration, C0, on nursing period, by a polynomial function Ctbf/C0=0.596+0.278t-0.0047t(2) which reliably predicts exposure to PCB 153 of breastfed infants, important for assessment of dose-outcome relationships. Adjustment of current serum concentrations to cord serum concentration improved validity of exposure assessment.

Polychlorinated biphenyls and selected organochlorine pesticides in serum of Slovak population from industrial and non-industrial areas.

The concentrations of indicator polychlorinated biphenyls (PCBs No. 28, 52, 101, 138, 153 and 180) and organochlorine pesticides (HCB, p,p'-DDE and p,p'-DDT) in 121 blood serum specimens collected from non-occupationally exposed adults living in contaminated and comparison areas were determined using high-resolution gas chromatography/electron capture detection (HRGC/ECD). The sum of the serum concentrations of the three most abundant PCB congeners (No. 138, 153 and 180) found in participants (N = 81) living in industrial areas near incinerators, metallurgical and chemical plants (Krompachy, Kosice, Nemecka and Sala) was significantly higher (p < 0.001) than in participants living in villages and towns without known sources causing persistent organic pollutant (POP) contamination (N = 40). Similarly, significant differences were observed for p,p'-DDE (p < 0.0001) and p,p'-DDT (p < 0.002). However, a Mann-Whitney U test between groups showed that the difference for HCB was not statistically significant (p = 0.089). Age was positively correlated with the sum of PCBs (No. 138, 153 and 180), HCB and the sum of p,p'-DDE and p,p'-DDT (p < 0.01 for all).

Prenatal and postnatal serum PCB concentrations and cochlear function in children at 45 months of age.

BACKGROUND: Some experimental and human data suggest that exposure to polychlorinated biphenyls (PCBs) may induce ototoxicity, though results of previous epidemiologic studies are mixed and generally focus on either prenatal or postnatal PCB concentrations exclusively. OBJECTIVES: Our aim was to evaluate the association between pre- and postnatal PCB concentrations in relation to cochlear status, assessed by distortion product otoacoustic emissions (DPOAEs), and to further clarify the critical periods in development where cochlear status may be most susceptible to PCBs. METHODS: A total of 351 children from a birth cohort in eastern Slovakia underwent otoacoustic testing at 45 months of age. Maternal pregnancy, cord, and child 6-, 16-, and 45-month blood samples were collected and analyzed for PCB concentrations. At 45 months of age, DPOAEs were assessed at 11 frequencies in both ears. Multivariate, generalized linear models were used to estimate the associations between PCB concentrations at different ages and DPOAEs, adjusting for potential confounders. RESULTS: Maternal and cord PCB-153 concentrations were not associated with DPOAEs at 45 months. Higher postnatal PCB concentrations at 6-, 16-, and 45-months of age were associated with lower (poorer) DPOAE amplitudes. When all postnatal PCB exposures were considered as an area-under-the-curve metric, an increase in PCB-153 concentration from the 25th to the 75th percentile was associated with a 1.6-dB SPL (sound pressure level) decrease in DPOAE amplitude (95% CI: -2.6, -0.5; p = 0.003). CONCLUSIONS: In this study, postnatal rather than maternal or cord PCB concentrations were associated with poorer performance on otoacoustic tests at age 45 months.

PCDDs, PCDFs, PCBs and OCPs in sediments from selected areas in the Slovak Republic.

Within our research project, 34 river bottom sediments were collected in 2006-2007 at five areas across Slovakia with industrial sources of persistent organic pollutants (Kosice, Krompachy, Nemecká, Sala, Nováky) and one background area (Starina). Sediments were analyzed for seven 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDDs) and 10 dibenzofurans (PCDFs), 12 dioxin-like and 6 indicator polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB) and 1,1,1,-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT) with 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE). Analytical procedure based on accelerated solvent extraction followed by a semi-automated clean-up and fractionation was used. Determination of target compounds was performed by HRGC-HRMS analysis. Total WHO toxic equivalent WHO1998-PCDD/F/dl-PCB-TEQ concentrations ranged from 0.26 to 559 pg TEQ g(-1) dry matter (dm), with a median 2.2 pg TEQ g(-1) dm. The sums of six indicator PCBs were in the range 0.56-1014 ng g(-1) dm, with a median 11.8 ng g(-1) dm. The concentrations of organochlorine pesticides HCB and p,p'-DDE/DDT varied from 0.15 to 34.8 ng g(-1) dm, with a median 0.91 ng g(-1) dm and 0.46-34.1 ng g(-1)dm, with a median 6.7 ng g(-1)dm, respectively. The most abundant congeners in all sediment samples among dioxins, furans and PCBs were OCDD, 1,2,3,4,6,7,8-HpCDF, PCB-118 and PCB-153.

Relative effect potency estimates of dioxin-like activity for dioxins, furans, and dioxin-like PCBs in adults based on two thyroid outcomes.

BACKGROUND: Toxic equivalency factors (TEFs) are an important component in the risk assessment of dioxin-like human exposures. At present, this concept is based mainly on in vivo animal experiments using oral dosage. Consequently, the current human TEFs derived from mammalian experiments are applicable only for exposure situations in which oral ingestion occurs. Nevertheless, these "intake" TEFs are commonly-but incorrectly-used by regulatory authorities to calculate "systemic" toxic equivalents (TEQs) based on human blood and tissue concentrations, which are used as biomarkers for either exposure or effect. OBJECTIVES: We sought to determine relative effect potencies (REPs) for systemic human concentrations of dioxin-like mixture components using thyroid volume or serum free thyroxine (FT4) concentration as the outcomes of interest. METHODS: We used a benchmark concentration and a regression-based approach to compare the strength of association between each dioxin-like compound and the thyroid end points in 320 adults residing in an organochlorine-polluted area of eastern Slovakia. RESULTS: REPs calculated from thyroid volume and FT4 were similar. The regression coefficient (ß)-derived REP data from thyroid volume and FT4 level were correlated with the World Health Organization (WHO) TEF values (Spearman r = 0.69, p = 0.01 and r = 0.62, p = 0.03, respectively). The calculated REPs were mostly within the minimum and maximum values for in vivo REPs derived by other investigators. CONCLUSIONS: Our REPs calculated from thyroid end points realistically reflect human exposure scenarios because they are based on chronic, low-dose human exposures and on biomarkers reflecting body burden. Compared with previous results, our REPs suggest higher sensitivity to the effects of dioxin-like compounds.

Anthropometric, socioeconomic, and maternal health determinants of placental transfer of organochlorine compounds.

The aim of this study was to relate placental transfer, quantified by the cord to maternal serum concentration ratio (C/M), of five organochlorine pesticides (OCP) hexachlorobenzene (HCB), ß-hexachlorocyclohexane (ß-HCH), γ-hexachlorocyclohexane (γ-HCH) , p,p'-DDT, p,p'-DDE and 15 polychlorinated biphenyl (PCB) congeners (28, 52, 101, 105, 114, 118, 123(+149), 138(+163), 153, 156(+171), 157, 167, 170, 180, and 189) to anthropometric, socioeconomic, and maternal health characteristics. We included into the study 1,134 births during the period 2002-2004 from two districts in eastern Slovakia with high organochlorine concentrations relative to other areas of the world. Only concentrations >LOD were taken into account. Variables as age, weight and height of mothers, parity, ethnicity, alcohol consumption, illness during pregnancy, smoking during pregnancy, hypertension, respiratory diseases, rheumatoid arthritis and diabetes mellitus, and birth weight were related to C/M. Results of regression analyses showed that C/M was predicted by several factors studied. Positive associations were observed for gestational alcohol consumption, fewer illnesses during pregnancy, maternal age, and maternal weight. Caucasians had a greater C/M compared to Romani for wet weight data of congeners 170 and 180 and in contrast C/M for HCB was greater in Romani. Our results show that drinking mothers compared to abstaining expose their fetuses not only to alcohol but to an increased level of several PCB congeners. A straightforward explanation of associations between C/M shifts and factors studied is very difficult, however, with regard to the high lipophilicity of OCPs and PCBs, changes in their kinetics probably reflect lipid kinetics.

PCDD/PCDF, dl-PCB and PBDE serum levels of Slovak general population.

Blood serum specimens from 81 non-occupationally exposed adults residing in four areas close to municipal and waste incinerators as well as metallurgical industry plant and 44 adult subjects coming from control area of Slovakia were analysed for polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), dioxin-like polychlorinated biphenyls (dl-PCBs) and polybrominated diphenylethers (PBDEs). The concentration of total WHO(98)TEQ PCDD/F/dl-PCBs in whole group of donors from areas where known sources causing dioxin contamination are present was significantly higher than in control group of donors (p<0.001). Correlation between the age of donors and PCDD/F and dl-PCB levels was confirmed (Spearman's r(PCDD/Fs)=0.543, r(dl-PCBs)=0.521, p<0.001). Furthermore, this study presents first results concerning the PBDE congeners in human serum of Slovak general population. The total concentration (congeners 28, 47, 99, 100, 153, 154, 183) in control group was approximately 1.5-times higher in comparison to that of residents coming from areas with supposed environmental pollution. The most abundant congeners in all samples were BDE-47 and BDE-153 with median values of 0.24 ng g(-1) lipid and 0.23ngg(-1) lipid, respectively. The positive association between PBDE values and age of donors was not found.

Pre- and postnatal polychlorinated biphenyl concentrations and longitudinal measures of thymus volume in infants.

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.

Maternal and early postnatal polychlorinated biphenyl exposure in relation to total serum immunoglobulin concentrations in 6-month-old infants.

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.

Half-lives of serum PCB congener concentrations in environmentally exposed early adolescents.

The aim was to determine half-life of six most abundant PCB congeners in the body of early adolescents. In 304 environmentally exposed children, PCB serum concentration was determined at the age of 8 and 12years. Half-life was determined for each child assuming exponential decrease or for the whole cohort using multiple regression. Results obtained by both approaches were in agreement. PCB reuptakes corrupting half-life estimates for each child and each congener were evaluated. If one of the serum PCB concentration values fell below the level of detection (LOD) the pair was excluded and if PCB half-life value exceeded the arbitrary value of 30years. The following median half-lives in years 4.46, 10.59, 9.7, 4.7, 9.1 and 9.8 were obtained for PCB congeners 118, 138(+163), 153, 156(+171), 170 and 180, respectively. The elimination half-life values were not systematically related to PCB serum concentration at any examination age. Between half-life values, percentage of children with significant reuptakes and PCB congener abundance in serum were found significant associations.