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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, β = −23.6), while adjusting for PCB-153 and sex. Significant negative associations were observed for BDE-153 serum concentrations (p = 0.002, β = −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 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.

Phthalates are environmental pollutants that can enter the human body by ingestion, inhalation and dermal absorption. Food constitutes the most important source of human exposure to these chemicals. The aim of our study was the biological monitoring of exposure to eight phthalate metabolites in children (n=107), 10–12 years of age, living in eastern Slovakia. Additionally, we analysed some associations between anthropometric measures, questionnaire data (i.e. eating and drinking habits, practice of personal care products) and concentrations of phthalate metabolites. Because of the short half-life of phthalates, within 24–48 h, we used 24-h recalls to assess dietary intakes. We used high-performance liquid chromatography and tandem mass spectrometry for the analysis of spot urine samples to determine concentrations of phthalate metabolites mono-ethyl phthalate (MEP), mono-n-butyl phthalate, mono-iso-butyl phthalate, mono-benzyl phthalate (MBzP), mono (2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), mono-carboxy pentyl and mono (2-ethylhexyl) phthalate (MEHP). We found statistically significant association between consumer practices and concentration of some phthalate metabolites, concretely consumption of milk and dairy products with MBzP and margarine with MEP (p

Introduction: To date, the evidence for an association between perfluoroalkyl substances (PFAS) exposure and attention deficit and hyperactivity disorder (ADHD) is inconclusive. Objective: We investigated the association between early life exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), and ADHD in a collaborative study including nine European population-based studies, encompassing 4,826 mother-child pairs. Methods: Concentrations of PFOS and PFOA were measured in maternal serum/plasma during pregnancy, or in breast milk, with different timing of sample collection in each cohort. We used a validated pharmacokinetic model of pregnancy and lactation to estimate concentrations of PFOS and PFOA in children at birth and at 3, 6, 12, and 24 months of age. We classified ADHD using recommended cutoff points for each instrument used to derive symptoms scores. We used multiple imputation for missing covariates, logistic regression to model the association between PFAS exposure and ADHD in each study, and combined all adjusted study-specific effect estimates using random-effects meta-analysis. Results: A total of 399 children were classified as having ADHD, with a prevalence ranging from 2.3% to 7.3% in the studies. Early life exposure to PFOS or PFOA was not associated with ADHD during childhood [odds ratios (ORs) ranging from 0.96 (95% CI: 0.87, 1.06) to 1.02 (95% CI: 0.93, 1.11)]. Results from stratified models suggest potential differential effects of PFAS related to child sex and maternal education. Conclusion: We did not identify an increased prevalence of ADHD in association with early life exposure to PFOS and PFOA. However, stratified analyses suggest that there may be an increased prevalence of ADHD in association with PFAS exposure in girls, in children from nulliparous women, and in children from low-educated mothers, all of which warrant further exploration. https://doi.org/10.1289/EHP5444. This research was primarily supported by a grant from the European Community’s Seventh Framework Program (FP7/2007–2013) under grant agreement Developmental Neurotoxicity Assessment of Mixtures in Children (DENAMIC) no. 282957. M.-A.V. is the recipient of a Research Scholars J1 Award from the Fonds de recherche du Québec–Santé. Norwegian Human Milk Study (HUMIS) research was funded by a grant from the Norwegian Research Council, under the NEVRINOR program grant agreement no. 226402; by PROTECTion against Endocrine Disruptors: Detection, mixtures, health effects, risk assessment and communication, and by European Union (EU) Horizon 2020 Marie Skłodowska-Curie Actions Innovative Training Networks–European Training Network no. 722634. We thank Anteneh Desalegn for his work in the HUMIS biobank. The study was approved by the Regional Ethics Committee for Medical Research in Norway (ref. S-02122) and the Norwegian Data Inspectorate (refs. 2002/1398), and participation did not occur until after informed consent was obtained. The Infancia y Medio Ambiente (INMA) study was funded by grants from the EU: NEWGENERIS FP6-2003-Food-3-A-016320, FP7-ENV-2011 cod 282957, HEALTH.2010.2.4.5-1; and by grants from Spain: Instituto de Salud Carlos III (Red INMA G03/176 and CB06/02/0041, FIS-FEDER:PI 03/1615, PI04/1509, PI04/1112, PI04/1436, PI04/1931, PI/04/2018, PI05/1079, PI05/1052, PI06/0867, PI06/1213, PI07/0314, PI/08/1151, PI09/02647, FIS-PI041436, FIS-PI081151, FISS-PI042018, FISS-PI09/02311, FISPI06/0867 FIS-PS09/00090, FIS-PI07/0252, PS09/00090, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, PI17/00663 and Miguel Servet-FEDER: CP11/00178, MS13/00054, and MSII16/00051), Generalitat de Catalunya-CIRIT 1999SGR 00241, La Fundació La Marató de TV3 (090430), Alicia Koplowitz Foundation 2017, Conselleria de Sanitat Generalitat Valenciana, Department of Health of the Basque Government (2005111093 and 2009111069), Provincial Government of Gipuzkoa (DFG06/004 and DFG08/001), Obra Social Cajastur, Universidad de Oviedo, Consejería de Salud de la Junta de Andalucía (grant no. 183/07), EU Commission (QLK4-1999-01422, QLK4-2002-00603, and CONTAMED FP7-ENV-212502), and Fundación Roger Torné. Global Health Institute Barcelona (ISGlobal) is a member of the CERCA Programme, Generalitat de Catalunya. A full roster of the INMA Project Investigators can be found at http://www.proyectoinma.org/presentacion-inma/listadoinvestigadores/en_listado-investigadores.html. The INUENDO study was funded by the European Commission’s Seventh and Fifth Framework Programmes (FP7-ENV-2008-1-226217 and QLK4-CT-2001-00202). The polychorinated biphenyl (PCB) cohort was funded by the U.S. National Institutes of Health (grants R01 CA096525 and R03 TW007152), the EU Seventh Framework Programme FP7/2007-2023 (grant agreement OBELIX, no. 227391), Slovak Research and Development Agency (grants APVT-21-016804, APVV-0571-12, APVV-0444-11), and by the ITMS project (no. 26240120033) based on the supporting operational research and development program from the European Regional Development Fund. This research was primarily supported by a grant from the European Community’s Seventh Framework Program (FP7/2007–2013) under grant agreement Developmental Neurotoxicity Assessment of Mixtures in Children (DENAMIC) no. 282957. M.-A.V. is the recipient of a Research Scholars J1 Award from the Fonds de recherche du Québec–Santé. Norwegian Human Milk Study (HUMIS) research was funded by a grant from the Norwegian Research Council, under the NEVRINOR program grant agreement no. 226402; by PROTECTion against Endocrine Disruptors: Detection, mixtures, health effects, risk assessment and communication, and by European Union (EU) Horizon 2020 Marie Skłodowska-Curie Actions Innovative Training Networks–European Training Network no. 722634. We thank Anteneh Desalegn for his work in the HUMIS biobank. The study was approved by the Regional Ethics Committee for Medical Research in Norway (ref. S-02122) and the Norwegian Data Inspectorate (refs. 2002/1398), and participation did not occur until after informed consent was obtained. The Infancia y Medio Ambiente (INMA) study was funded by grants from the EU: NEWGENERIS FP6-2003-Food-3-A-016320, FP7-ENV-2011 cod 282957, HEALTH.2010.2.4.5-1; and by grants from Spain: Instituto de Salud Carlos III (Red INMA G03/176 and CB06/02/0041, FIS-FEDER:PI 03/1615, PI04/1509, PI04/1112, PI04/1436, PI04/1931, PI/04/2018, PI05/1079, PI05/1052, PI06/0867, PI06/1213, PI07/0314, PI/08/1151, PI09/02647, FIS-PI041436, FIS-PI081151, FISS-PI042018, FISS-PI09/02311, FISPI06/0867 FIS-PS09/00090, FIS-PI07/0252, PS09/00090, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, PI17/00663 and Miguel Servet-FEDER: CP11/00178, MS13/00054, and MSII16/00051), Generalitat de Catalunya-CIRIT 1999SGR 00241, La Fundació La Marató de TV3 (090430), Alicia Koplowitz Foundation 2017, Conselleria de Sanitat Generalitat Valenciana, Department of Health of the Basque Government (2005111093 and 2009111069), Provincial Government of Gipuzkoa (DFG06/004 and DFG08/001), Obra Social Cajastur, Universidad de Oviedo, Consejería de Salud de la Junta de Andalucía (grant no. 183/07), EU Commission (QLK4-1999-01422, QLK4-2002-00603, and CONTAMED FP7-ENV-212502), and Fundación Roger Torné. Global Health Institute Barcelona (ISGlobal) is a member of the CERCA Programme, Generalitat de Catalunya. A full roster of the INMA Project Investigators can be found at http://www.proyectoinma.org/presentacion-inma/listadoinvestigadores/en_listado-investigadores.html. The INUENDO study was funded by the European Commission’s Seventh and Fifth Framework Programmes (FP7-ENV-2008-1-226217 and QLK4-CT-2001-00202). The polychorinated biphenyl (PCB) cohort was funded by the U.S. National Institutes of Health (grants R01 CA096525 and R03 TW007152), the EU Seventh Framework Programme FP7/2007-2023 (grant agreement OBELIX, no. 227391), Slovak Research and Development Agency (grants APVT-21-016804, APVV-0571-12, APVV-0444-11), and by the ITMS project (no. 26240120033) based on the supporting operational research and development program from the European Regional Development Fund.

The aim of this study was to examine the hypothesis that organochlorine pesticides (OCPs), hexachlorobenzene (HCB), β-hexachlorocyclohexane (β-HCH), and 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (p,p'-DDT) and its metabolite 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (p,p'- DDE) are ototoxic to humans. A multivariate general linear model was designed, in which the statistical relation between blood serum concentrations of HCB, β-HCH, p,p'-DDT, or p,p'-DDE at different ages (at birth, 6, 16, and 45 months) and the distortion product otoacoustic emissions (DPOAEs) was treated as multivariate outcome variables. Polychlorinated biphenyl (PCB) congeners and OCPs were strongly correlated in serum of children from our cohort. To ascertain that the association between DPOAEs at a given frequency and concentration of a pesticide is not influenced by PCBs or other OCP also present in serum, we calculated benchmark concentrations (BMCs) relating DPOAEs to a serum pesticide alone and in presence of confounding PCB-153 or other OCPs. We found that BMCs relating DPOAEs to serum pesticides are not affected by confounders. DPOAE amplitudes were associated with serum OCPs at all investigated time intervals, however, in a positive way with prenatal exposure and in a negative way with all postnatal exposures. We observed tonotopicity in the association of pesticides with amplitude of DPOAEs as its strength was frequency dependent. We conclude that exposure to OCPs in infancy at environmental concentrations may be associated with hearing deficits.

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.

International audience; Background - Attention-deficit/hyperactivity disorder (ADHD) is increasing worldwide for reasons largely unknown and environmental chemicals with neurotoxic properties, such as persistent organic pollutants (POPs), have been proposed to play a role. We investigated the association between prenatal and postnatal exposure to polychlorinated biphenyl-153 (PCB-153), p-p´-dichlorodiphenyldichloroethylene (p-p'-DDE) and hexachlorobenzene (HCB) and ADHD in childhood. Methods - We pooled seven European birth cohort studies encompassing 4437 mother-child pairs from the general population with concentrations of PCB-153, p-p´-DDE and HCB measured in cord blood, maternal blood or milk. We then calculated prenatal (birth) and postnatal (3, 6, 12 and 24 months) POP concentrations using a pharmacokinetic model. The operational definition of ADHD varied across cohorts and ranged from doctor diagnosis obtained from patient registries to maternal or teachers reports. We used multilevel (mixed) logistic regression models to estimate the associations between exposure to POPs at birth, 3, 6, 12 and 24 months and ADHD. Results - The global prevalence of ADHD in our study was 6%. The mean age at assessment of ADHD was 5.8 years (range: 3.8-9.5 years). We found no association between exposure to PCB-153, p-p´-DDE and HCB at any age point between birth and 24 months and ADHD, in the pooled analyses (pooled odds ratios ranging from 1.00 to 1.01). A number of sensitivity analyses gave basically the same results. Conclusions - In the largest study to date of 4437 children in seven European birth cohorts, we did not observe any association between either pre- or postnatal exposure (up to 24 months) to PCB-153, p-p´-DDE and HCB and the risk of ADHD before the age of 10 years.

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 (β)-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.

Background: Epidemiological studies have demonstrated the ototoxic effects of exposure to polychlorinated biphenyls (PCBs). In a previous study, this effect was attributed to the PCB postnatal seru...

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 (

The chemical composition of persistent organic pollutants (POPs) in the environment is not uniform throughout the world, and these contaminants contain many structurally different lipophilic compounds. In a well-defined study cohort in the Slovak Republic, the POP chemicals present in the peripheral blood of exposed children were chemically analyzed. The chemical analysis data revealed that the relative concentration and profile of structurally different organic pollutants, including polychlorinated biphenyls (PCBs), 2,2′-bis(4-chlorophenyl)-1,1-dichloroethylene (p,p′-DDE), 2,2′-bis(4-chlorophenyl)-1,1,1-trichloro-ethane (p,p′-DDT), hexachlorobenzene (HCB) and β-hexachlorocyclohexane (β-HCH), may vary from individual to individual, even within the same exposure area. These chemicals can be broadly classified into two groups. The first group, the PCB congeners, primarily originated from industrial compounds and their byproducts. The second group of compounds originated from or was commonly used in the agricultural sector (e.g., DDT, HCB). The objective of this study was to examine the effects of the two POP exposure profiles on gene expression. For the study population, we selected pre-pubertal girls (mean age of 46.2±1.4 months) with high POP concentrations in their blood (>75% tile of total POP) and classified them in the high ‘PCB’ group when the total PCB concentration was significantly higher than the total concentration of other POP components and in the ‘Other Than PCB’ (OTP) group, when the total PCB concentration was significantly lower than the concentration of the other major POP constituents. A matched control group of girls (

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 12 years. 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 30 years. 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.

Objective The aim of this normative study was to examine cochlear status and possible ear asymmetry and gender effect in transient evoked and distortion product otoacoustic emissions in a group of healthy 12-year-old children in Slovakia. Methods Two hundred and twenty-nine 12-year-old children from Slovakia with normal hearing were included in this study. Adolescents with acute infection, abnormal otoscopic findings and abnormal tympanometry were excluded. Pure tone audiometry was performed in standard conditions in a sound proof room. Recordings of transient evoked (TE) and distortion product otoacoustic emissions (DPOAEs) were performed using an ILO 292 USB Echoport. Parameters of hearing thresholds and OAEs were compared using correlation analysis and Wilcoxon test. Results We found highly statistically significant associations between the hearing thresholds for the left and right ears. When comparing pure tone audiometry with OAEs no significant correlation was found. In TEOAE a significant gender effect and side effect in TEOAE SNR were found. On the other hand there was no side effect in TEOAE response level. In DPOAE neither gender nor side effects were determined. Conclusions This is the first comprehensive information on cochlear status among Slovak adolescents. The TEOAEs were significantly higher in girls than boys, but the ear asymmetry in TEOAE was not significant. For DPOAE responses ear asymmetry and gender did not play a role. The data obtained are a basis for population hearing screening, especially for hearing screening programs in infants and children in Slovakia. Moreover data from particular age group represent a link between data from infants and adults.

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 (β = −2.27; p = 0.01) and PDI (β = −4.50; p = 0.004). Also, maternal 4-OH-CB-107 was significantly associated with lower MDI (β = −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.

The objective of this cross-sectional epidemiological study was to assess if long-term exposure to polychlorinated biphenyls (PCBs) is associated with hearing impairment. Four hundred and thirty-three children aged 8-9 years residing in an area polluted by PCBs in Eastern Slovakia were examined otoscopically, tympanometrically and by pure tone audiometry. PCB levels in their serum were determined by gas chromatography. Transient otoacoustic emissions (TEOAE) were measured in a subgroup of 161 children. The mean of the sum of PCB concentrations in serum was 528.2ng/g serum lipids (median 321ng/g serum lipids). Serum PCB concentrations were associated with an increase of hearing threshold at low frequencies and a negative correlation between serum PCBs and the amplitude of TEOAE response was observed in the uppermost tertile of children grouped with regard to serum PCBs, not related to thyroid hormone levels. It was concluded that long-term environmental exposure to PCBs is associated with subclinical but diagnosable hearing deficits.

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 Strážske 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.

Simple reaction time (SRT) has been studied in children exposed to polychlorinated biphenyls (PCBs), with variable results. In the current work we examined SRT in 146 boys and 161 girls, aged 8.53 ± 0.65 years (mean ± SD), exposed to PCBs in the environment of eastern Slovakia. We divided the children into tertiles with regard to increasing PCB serum concentration. The mean ± SEM serum concentration of the sum of 15 PCB congeners was 191.15 ± 5.39, 419.23 ± 8.47, and 1315.12 ± 92.57 ng/g lipids in children of the first, second, and third tertiles, respectively. We created probability distribution plots for each child from their multiple trials of the SRT testing. We fitted response time distributions from all valid trials with the ex-Gaussian function, a convolution of a normal and an additional exponential function, providing estimates of three independent parameters μ, σ, and τ. μ is the mean of the normal component, σ is the standard deviation of the normal component, and τ is the mean of the exponential component. Group response time distributions were calculated using the Vincent averaging technique. A Q-Q plot comparing probability distribution of the first vs. third tertile indicated that deviation of the quantiles of the latter tertile from those of the former begins at the 40th percentile and does not show a positive acceleration. This was confirmed in comparison of the ex-Gaussian parameters of these two tertiles adjusted for sex, age, Raven IQ of the child, mother's and father's education, behavior at home and school, and BMI: the results showed that the parameters μ and τ significantly (p ≤ 0.05) increased with PCB exposure. Similar increases of the ex-Gaussian parameter τ in children suffering from ADHD have been previously reported and interpreted as intermittent attentional lapses, but were not seen in our cohort. Our study has confirmed that environmental exposure of children to PCBs is associated with prolongation of simple reaction time reflecting impairment of cognitive functions.

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

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

A cross-sectional clinical evaluation was performed on 395 children aged 9-10 yr residing in Bratislava, Republic of Slovakia, to examine the potential adverse effects of low lead levels in blood (PbB) on neuromotor and cognitive performance. Eight clinical evaluations comprised of neuromotor (simple reaction time, Vienna, tapping test) and cognitive tests (Benton, Bender, Raven, and WISC1 and 2) were conducted. Whole blood lead levels served as the surrogate for lead body-burden levels. The mean PbB of the study population was 36.5 ug/L (SD-16.2). A statistically significant negative association between PbB and global intelligence (Raven, p

Background In bird cohort studies have been observed that low levels of polychlorinated biphenyls (PCBs) have a negative effects on early cognitive development in children. More recent studies supp...

Background Human milk is an important carrier of PCBs and lactational transfer represents the primary route of PCB exposure to developing mammals. A measure of exposure of infants is the amount tak...

Investigators have typically relied on a single or few discrete time points as measures of polychlorinated biphenyl (PCB) body burden, however health effects are more likely to be the result of integrative exposure in time, optionally expressed as an area under the time curve (AUC) of PCB serum concentration. Using data from a subgroup of 93 infants from a birth cohort in eastern Slovakia—a region highly polluted by PCBs—we fit a system type model, customized to our longitudinal measures of serum PCB concentrations in cord, 6, 16, and, 45 month blood specimens. The most abundant congener, PCB 153, was chosen for modeling purposes. In addition to currently used methods of exposure assessment, our approach estimates a concentration time profile for each subject, taking into account mean residence time of PCB 153 molecules in the body, duration of breast feeding, hypothetical PCB 153 concentration in steady-state without breast feeding and alternately without normal food intake. Hypothetical PCB 153 concentration in steady-state without normal food intake correlates with AUC (r=0.84, p

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.

biphenyls (PCBs) by chemical structure and activity in a birth cohort Hye-Youn Park , Irva Hertz-Picciotto , Eva Sovcikova , Anton Kocan , Tomas Trnovec b Divisions of Epidemiology, and of Environmental and Occupational Health, Department of Public Health Sciences, School of Medicine, University of California, Davis, 95616, USA Department of Toxic Organic Pollutants, Slovak Medical University, Bratislava, Slovakia NeuroToxicology xxx (2009) xxx–xxx

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 ( χ 2 = 8.35; p = 0.03) according to their serum PCB concentration (group 0: 600 ng PCBs g −1 serum lipids). The proportion of permanent teeth affected with any enamel defect was significantly higher in higher exposed children ( χ 2 = 7.237; p = 0.027). Furthermore, the extent of the enamel defects was also greater ( χ 2 = 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.