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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.

Per-and polyfluoroalkyl substances (PFAS) are widespread pollutants that may impact youth adiposity patterns. We investigated cross-sectional associations between PFAS and body mass index (BMI) in teenagers/adolescents across nine European countries within the Human Biomonitoring for Europe (HBM4EU) initiative. We used data from 1957 teenagers (12-18 yrs) that were part of the HBM4EU aligned studies, consisting of nine HBM studies (NEBII, Norway; Riksmaten Adolescents 2016-17, Sweden; PCB cohort (follow-up), Slovakia; SLO CRP, Slovenia; CROME, Greece; BEA, Spain; ESTEBAN, France; FLEHS IV, Belgium; GerES V-sub, Germany). Twelve PFAS were measured in blood, whilst weight and height were measured by field nurse/physician or self-reported in ques-tionnaires. We assessed associations between PFAS and age-and sex-adjusted BMI z-scores using linear and logistic regression adjusted for potential confounders. Random-effects meta-analysis and mixed effects models were used to pool studies. We assessed mixture effects using molar sums of exposure biomarkers with toxicological/structural similarities and quantile g-computation. In all studies, the highest concentrations of PFAS were PFOS (medians ranging from 1.34 to 2.79 mu g/L). There was a tendency for negative associations with BMI z-scores for all PFAS (except for PFHxS and PFHpS), which was borderline significant for the molar sum of [PFOA and PFNA] and significant for single PFOA [beta-coefficient (95% CI) per interquartile range fold change =-0.06 (-0.17, 0.00) and-0.08 (-0.15,-0.01), respectively]. Mixture assessment indicated similar negative associations of the total mixture of [PFOA, PFNA, PFHxS and PFOS] with BMI z-score, but not all compounds showed associations in the same direction: whilst [PFOA, PFNA and PFOS] were negatively associated, [PFHxS] associated positively with BMI z-score. Our results indicated a tendency for associations of relatively low PFAS concentrations with lower BMI in European teenagers. More prospective research is needed to investigate this potential relationship and its implications for health later in life., European Commission 733032, Swedish Research Council European Commission 2017-00822

The risk of cancer due to PCB exposure in humans is highly debated. In eastern Slovakia, high exposure of the population to organochlorines (especially PCBs) was associated with various disease and disorder pathways, viz., endocrine disruption, metabolic disorder & diabetes, and cancer, thereby disturbing several cellular processes, including protein synthesis, stress response, and apoptosis. We have evaluated a Slovak cohort (45-month children, at lower and higher levels of PCB exposure from the environment) for disease and disorder development to develop early disease cancer biomarkers that could shed new light on possible mechanisms for the genesis of cancers under such chemical exposures, and identify potential avenues for prevention. Microarray studies of global gene expression were conducted from the 45-month-old children on the Affymetrix platform followed by Ingenuity Pathway Analysis (IPA®) to associate the affected genes with their mechanistic pathways. High-throughput qRT-PCR TaqMan low-density array (TLDA) was performed to further validate the selected genes on the whole blood cells of the most highly exposed children from the study cohort (n = 71). TP53, MYC, BCL2, and LRP12 differential gene expressions suggested strong relationships between potential future tumor promotion and PCB exposure in Slovak children. The IPA analysis further detected the most important signaling pathways, including molecular mechanism of cancers, prostate cancer signaling, ovarian cancer signaling, P53 signaling, oncostatin M signaling, and their respective functions (viz., prostate cancer, breast cancer, progression of tumor, growth of tumor, and non-Hodgkin’s disease). The results suggest that PCB exposures, even at the early age of these children, may have lifelong consequences for the future development of chronic diseases.

Polychlorinated biphenyls (PCBs) are one of the original twelve classes of toxic chemicals covered by the Stockholm Convention on Persistent Organic Pollutants (POP), an international environmental treaty signed in 2001. PCBs are present in the environment as mixtures of multiple isomers at different degree of chlorination. These compounds are manmade and possess useful industrial properties including extreme longevity under harsh conditions, heat absorbance, and the ability to form an oily liquid at room temperature that is useful for electrical utilities and in other industrial applications. They have been widely used for a wide range of industrial purposes over the decades. Despite a ban in production in 1979 in the US and many other countries, they remain persistent and ubiquitous in environment as contaminants due to their improper disposal. Humans, independent of where they live, are therefore exposed to PCBs, which are routinely found in random surveys of human and animal tissues. The prolonged exposures to PCBs have been associated with the development of different diseases and disorders, and they are classified as endocrine disruptors. Due to its ability to interact with thyroid hormone, metabolism and function, they are thought to be implicated in the global rise of obesity diabetes, and their potential toxicity for neurodevelopment and disorders, an example of gene by environmental interaction (GxE). The current review is primarily intended to summarize the evidence for the association of PCB exposures with increased risks for metabolic dysfunctions and neurobehavioral disorders. In particular, we present evidence of gene expression alterations in PCB-exposed populations to construct the underlying pathways that may lead to those diseases and disorders in course of life. We conclude the review with future perspectives on biomarker-based research to identify susceptible individuals and populations.

Background and aims Our earlier gene-expression studies with a Slovak PCBs-exposed population have revealed possible disease and disorder development in accordance with epidemiological studies. The present investigation aimed to develop an in vitro model system that can provide an indication of disrupted biological pathways associated with developing future diseases, well in advance of the clinical manifestations that may take years to appear in the actual human exposure scenario. Methods We used human Primary Blood Mononuclear Cells (PBMC) and exposed them to a mixture of human equivalence levels of PCBs (PCB-118, -138, -153, -170, -180) as found in the PCBs-exposed Slovak population. The microarray studies of global gene expression were conducted on the Affymetrix platform using Human Genome U133 Plus 2.0 Array along with Ingenuity Pathway Analysis (IPA) to associate the affected genes with their mechanistic pathways. High-throughput qRT-PCR Taqman Low Density Array (TLDA) was done to further validate the selected 6 differentially expressed genes of our interest, viz. , ARNT, CYP2D6, LEPR, LRP12, RRAD, TP53, with a small population validation sample ( n =71). Results Overall, we revealed a discreet gene expression profile in the experimental model that resembled the diseases and disorders observed in PCBs-exposed population studies. The disease pathways included endocrine system disorders, genetic disorders, metabolic diseases, developmental disorders, and cancers, strongly consistent with the evidence from epidemiological studies. Interpretation These gene finger prints could lead to the identification of populations and subgroups at high risk for disease, and can pose as early disease biomarkers well ahead of time, before the actual disease becomes visible.

Recently the prevalence of obesity has increased dramatically across much of the world. Obesity, as a complex, multifactorial disease, and its health consequences probably result from the interplay of environmental, genetic, and behavioral factors. Several lines of evidence support the theory that obesity is programmed during early development and that environmental exposures can play a key role. We therefore hypothesize that the current epidemic might associated with the influence of chemical exposures upon genetically controlled developmental pathways, leading to metabolic disorders. Some environmental chemicals, such as PCBs and pesticide residues, are widespread in food, drinking water, soil, and they exert multiple effects including estrogenic on cellular processes; some have been shown to affect the development of obesity, insulin resistance, type 2 diabetes, and metabolic syndrome. To bring these lines of evidence together and address an important health problem, this narrative review has been primarily designed to address PCBs exposures that have linked with human disease, obesity in particular, and to assess the effects of PCBs on gene expression in a highly-exposed population. The results strongly suggest that further research into the specific mechanisms of PCBs-associated diseases is warranted.

Background: Despite experimental evidence that lactational exposure to persistent organic pollutants (POPs) can impact health, results from epidemiologic studies are inconclusive. Inconsistency across studies may reflect the inability of current methods to estimate children’s blood levels during specific periods of susceptibility. Objectives: We developed a toxicokinetic model to simulate blood POP levels in children from two longitudinal birth cohorts and aimed to validate it against blood levels measured at 6, 16, and 45 months of age. Methods: The model consisted of a maternal and a child lipid compartment connected through placental diffusion and breastfeeding. Simulations were carried out based on individual physiologic parameters; duration of breastfeeding; and levels of POPs measured in maternal blood at delivery, cord blood, or breast milk. Model validity was assessed through regression analyses of simulated against measured blood levels. Results: Simulated levels explained between 10% and 83% of measured blood levels depending on the cohort, the compound, the sample used to simulate children’s blood levels, and child’s age when blood levels were measured. Model accuracy was highest for estimated blood POP levels at 6 months based on maternal or cord blood levels. However, loss in model precision between the 6th and the 45th month was small for most compounds. Conclusions: Our validated toxicokinetic model can be used to estimate children’s blood POP levels in early to mid-childhood. Estimates can be used in epidemiologic studies to evaluate the impact of exposure during hypothesized postnatal periods of susceptibility on health.

The goal of the present study is to understand the probable molecular mechanism of toxicities and the associated pathways related to observed pathophysiology in high PCB-exposed populations. We have performed a microarray-based differential gene expression analysis of children (mean age 46.1 months) of Central European descent from Slovak Republic in a well-defined study cohort. The subset of children having high blood PCB concentrations (>75 percentile) were compared against their low PCB counterparts (

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.

Exposure to polychlorinated biphenyls (PCBs) during pre-natal and early life can alter normal immune system development. Blood specimens from newborns, 6-, and 16-month-old infants were collected in the Michalovce and Svidnik/Stropkov districts, areas with, respectively, high and low environmental PCB contamination, and lymphocyte receptor expression was evaluated by multi-color flow cytometry. The results indicate that the percentage of lymphoid dendritic cells (DC) and naive/resting T-lymphocytes were significantly increased at 6-months in Michalovce as compared to the same cell types in cord blood samples (p < 0.001), whereas natural regulatory T-lymphocytes and suppressor inducer T-lymphocytes were reduced (p < 0.001). Overall, a positive linear correlation of terminally differentiated effector memory (TEM) T-lymphocyte population with age, but a negative linear correlation for myeloid DC from birth to 6-months in both regions were found. Michalovce samples indicated significantly higher expression of memory T-lymphocytes (birth, 6(th), and 16(th) month), TEM T-lymphocytes (birth and 6(th) month), and lymphoid DC (6(th) month) compared to the Svidnik/Stropkov regions. After adjustment for relevant covariates, such as maternal age, parity, season of birth, breastfeeding, birth weight, and gender, the myeloid DC, suppressor inducer T-lymphocytes, truly naive helper/inducer T-lymphocytes, and TEM T-lymphocytes remained significantly different between districts in cord blood samples. The multivariate analysis models for 6- and 16-month samples showed district differences in all cellular determinants, except for lymphoid DC and macrophage-like cells. This study provides the first evidence that pre-natal and early post-natal exposure to PCBs affects the dynamics of cell surface receptor expression on lymphoid DC and DC-like cells, suggesting impaired immunologic development following pre-natal and early post-natal PCB exposure.

Immune system development, particularly in the pre-natal and early post-natal periods, has far-reaching health consequences during childhood, as well as throughout life. Exposure to poly-chlorinated biphenyls (PCBs) during pre-natal and early life has been previously associated with changes in the incidence of infectious and allergic diseases in children, and humoral immunity alterations. Lymphocyte immunophenotyping is an important tool in the diagnosis of immunologic and hematologic disorders. This study used a lysed whole blood method for analysis of lymphocyte sub-populations in samples from children born and living in two districts: a highly-contaminated area (Michalovce) and one (Svidnik/Stropkov) with ≈ 2-fold lower environmental PCB levels. The percentages of B-lymphocytes (CD19(+)), activated HLADR(+)CD19(+) cells, and CD8(+) T-lymphocytes significantly increased at 6- and 16-months-of-age in both selected regions as compared to in cord blood values (p0.001). Levels of CD3(+) cells increased significantly (from 61 to 65%) in samples from Michalovce (p0.01). Levels of CD4(+) T-lymphocytes declined 10% among 16-month-olds in both regions (Michalovce at p0.001 and Svidnik/Stropkov at p0.01). Natural killer (NK) cell levels decreased 50% in Michalovce 6- and 16-month-old children and 42% among 6-month-olds in Svidnik/Stropkov (p0.001). Compared with the less-contaminated region, Michalovce samples showed significantly higher expression of CD3(+) T-lymphocytes, B-lymphocytes, and activated B-lymphocytes, whereas NK cells were less expressed. Even after adjustment for selected covariates, e.g., maternal cigarette smoking, age, parity, ethnicity, birth weight, and gender of infant, the levels of CD19(+), HLADR(+)CD19(+), and CD3(-)CD(16 + 56)(+) cells were seen to remain significantly different between the districts. These results showed that early-life environmental PCB exposure was associated with fluctuations in major lymphocyte subsets in children, suggesting that there is a post-natal immune system response to PCB exposures.

Objectives: Exposure to high concentrations of persistent organochlorines may cause fetal toxicity, but the evidence at low exposure levels is limited. Large studies with substantial exposure contrasts and appropriate exposure assessment are warranted. Within the framework of the EU (European Union) ENRIECO (ENvironmental Health RIsks in European Birth Cohorts) and EU OBELIX (OBesogenic Endocrine disrupting chemicals: LInking prenatal eXposure to the development of obesity later in life) projects, we examined the hypothesis that the combination of polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE) adversely affects birth weight. Methods: We used maternal and cord blood and breast milk samples of 7,990 women enrolled in 15 study populations from 12 European birth cohorts from 1990 through 2008. Using identical variable definitions, we performed for each cohort linear regression of birth weight on estimates of cord serum concentration of PCB-153 and p,p´-DDE adjusted for gestational age and a priori selected covariates. We obtained summary estimates by meta-analysis and performed analyses of interactions. Results: The median concentration of cord serum PCB-153 was 140 ng/L (range of cohort medians 20484 ng/L) and that of p,p´-DDE was 528 ng/L (range of cohort medians 501,208 ng/L). Birth weight decreased with increasing cord serum concentration of PCB-153 after adjustment for potential confounders in 12 of 15 study populations. The meta-analysis including all cohorts indicated a birth weight decline of 150 g [95% confidence interval (CI): 250, 50 g] per 1-µg/L increase in PCB-153, an exposure contrast that is close to the range of exposures across the cohorts. A 1-µg/L increase in p,p´-DDE was associated with a 7-g decrease in birth weight (95% CI: 18, 4 g). Conclusions: The findings suggest that low-level exposure to PCB (or correlated exposures) impairs fetal growth, but that exposure to p,p´-DDE does not. The study adds to mounting evidence that low-level exposure to PCBs is inversely associated with fetal growth.

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.

Low-level exposure to polychlorinated biphenyl-153 (PCB-153) and dichlorodiphenyldichloroethylene (p-p′-DDE) can impair fetal growth; however, the exposure–response relationship and effect modifiers of such association are not well established. This study is an extension of an earlier European meta-analysis. Our aim was to explore exposure–response relationship between PCB-153 and p-p′-DDE and birth outcomes; to evaluate whether any no exposure–effect level and susceptible subgroups exist; and to assess the role of maternal gestational weight gain (GWG). We used a pooled dataset of 9377 mother–child pairs enrolled in 14 study populations from 11 European birth cohorts. General additive models were used to evaluate the shape of the relationships between organochlorine compounds and birth outcomes. We observed an inverse linear exposure–response relationship between prenatal exposure to PCB-153 and birth weight [decline of 194 g (95% CI −314, −74) per 1 μg/L increase in PCB-153]. We showed effects on birth weight over the entire exposure range, including at low levels. This reduction seems to be stronger among children of mothers who were non-Caucasian or had smoked during pregnancy. The most susceptible subgroup was girls whose mothers smoked during pregnancy. After adjusting for absolute GWG or estimated fat mass, a reduction in birth weight was still observed. This study suggests that the association between low-level exposure to PCB-153 and birth weight exists and follows an inverse linear exposure–response relationship with effects even at low levels, and that maternal smoking and ethnicity modify this association. Keywords: Biomarkers of exposure, Persistent organic pollutants, Polychlorinated biphenyls (PCBs), Dichlorodiphenyldichloroethylene (DDE), Birth weight

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. Citation: Jusko TA, Sisto R, Iosif AM, Moleti A, Wimmerová S, Lancz K, Tihányi J, Šovčíková E, Drobná B, Palkovičová L, Jurečková D, Thevenet-Morrison K, Verner MA, Sonneborn D, Hertz-Picciotto I, Trnovec T. 2014. Prenatal and postnatal serum PCB concentrations and cochlear function in children at 45 months of age. Environ Health Perspect 122:1246–1252; http://dx.doi.org/10.1289/ehp.1307473

Allergic diseases are on the rise in both prevalence and severity, especially in industrialized countries. The process of allergic sensitization needs an understanding of the role environmental factors play in its development. In addition to traditionally considered air pollutants, various persistent organochlorine pollutants, which accumulate in the human body over a lifetime via food intake, are toxic in humans. Placental contamination by chemicals may act as a biologic marker for the exposure of the mother or for the fetus via transplacental transfer. Placentas were collected from term deliveries in two Slovak regions. The samples were then analyzed for 21 selected organochlorine compounds. Specimens of cord blood from 2,050 neonates were gathered for the determination of levels of total immunoglobulin E (IgE). The regions were chosen according to their environmental characteristics: a city polluted with organic chemical industry versus a rural region devoid of industrial sources of pollution. In addition, data regarding the incidence rate of atopic eczema cases in the regions were considered. Comparisons between regions revealed that both the placental contamination with 16 of 21 organochlorine compounds and the cord serum IgE levels were significantly higher in the industrial region. The findings pointed to an association between organochlorine compounds and the higher levels of total IgE in newborns, signaling a higher allergic sensitization in the industrial region. This association was supported by the higher incidence rate of atopic eczema cases in the population registered in the industrial region. Images Figure 1

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.

Recently, it has become clear that the complexity of environmental health issues requires an approach that takes into account the complexities, interdependencies and uncertainties of the real world. An urgent issue that has surfaced is the need for accurate tools to better describe exposure characterization to environmental chemicals. By including human biomonitoring (HBM) data, a greater precision in exposure and associated risk estimates and more accurate doseresponse relationships may be achieved. A restricting issue still is the availability of reliable and comparable HBM data. The aim of the current study was twofold: (1) to find out whether it is practically feasible to collect raw, individual HBM data across Europe; and (2) to evaluate the comparability and use of these HBM data for environmental health impact assessment at a European scale. Blood-lead (B-Pb) was selected as the chemical of choice because of its long history as an environmental pollutant in HBM programs and its known public health relevance. Through literature search and identification of HBM experts across Europe, HBM programs that measured B-Pb were identified and asked to share individual data on age, gender and B-Pb levels. Following this request, more than 20,000 individual data points from 8 European countries were collected. Analysing these data made clear that it is difficult to use disparate data collections because of the inherent variability with respect to the gender and age of participants and calendar-years sampled. When these confounders were taken however, there was no additional variability in B-Pb distributions among different countries. It was concluded that while it is possible to collect HBM data from different sources across Europe, the need to get data from comparable (sub-)populations is essential for appropriate use and interpretation of HBM data for environmental health impact assessment.

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.

1 There is a variety of quantitative analytical data regarding the total concentrations of heavy metals in human placentae. However, little is known about sites of metal accumulation in the placental tissue structural zones in relation to the environment. In this study, the lead and the nickel particulate deposits in the placental chorionic plate, the chorionic villous tree and the basal plate, using tissue histochemical reactions for lead and nickel, have been estimated. The degree of metal contamination of placentae was assessed according to an arbitrary scale. Both metals have shown a common mode of accumulation in the placental tissue structural zones. Among the observed contaminated structures in the placental tissue, the syncytiotrophoblast was the most frequent site for lead and nickel particulate deposits. 2 The frequency distribution of both metals within the mentioned placental zones, using four metal contamination degrees, was determined. A heavily contaminated zone was found to be the chorionic villous tree, especially in samples from the industrial region. 3 A comparison between two Slovak regions (an industrial and a rural one) using statistical tests was performed. The frequency of samples without any lead occurrence in the chorionic villous tree was found to be 10% in the industrial region, and 16% in the rural region. Regarding the nickel deposits, the frequency of non-contaminated samples in the industrial region was 2%, whereas in the rural region 6%. A relationship between traffic related pollution and human placenta contamination was found in both investigated regions.