Genotoxic effects of occupational exposure to glass fibres - A human biomonitoring study.

As part of a large human biomonitoring study, we conducted occupational monitoring in a glass fibre factory in Slovakia. Shopfloor workers (n = 80), with a matched group of administrators in the same factory (n = 36), were monitored for exposure to glass fibres and to polycyclic aromatic hydrocarbons (PAHs). The impact of occupational exposure on chromosomal aberrations, DNA damage and DNA repair, immunomodulatory markers, and the role of nutritional and lifestyle factors, as well as the effect of polymorphisms in metabolic and DNA repair genes on genetic stability, were investigated. The (enzyme-modified) comet assay was employed to measure DNA strand breaks (SBs) and apurinic sites, oxidised and alkylated bases. Antioxidant status was estimated by resistance to H2O2-induced DNA damage. Base excision repair capacity was measured with an in vitro assay (based on the comet assay). Exposure of workers to fibres was low, but still was associated with higher levels of SBs, and SBs plus oxidised bases, and higher sensitivity to H2O2. Multivariate analysis showed that exposure increased the risk of high levels of SBs by 20%. DNA damage was influenced by antioxidant enzymes catalase and glutathione S-transferase (measured in blood). DNA repair capacity was inversely correlated with DNA damage and positively with antioxidant status. An inverse correlation was found between DNA base oxidation and the percentage of eosinophils (involved in the inflammatory response) in peripheral blood of both exposed and reference groups. Genotypes of XRCC1 variants rs3213245 and rs25487 significantly decreased the risk of high levels of base oxidation, to 0.50 (p = 0.001) and 0.59 (p = 0.001), respectively. Increases in DNA damage owing to glass fibre exposure were significant but modest, and no increases were seen in chromosome aberrations or micronuclei. However, it is of concern that even low levels of exposure to these fibres can cause significant genetic damage.

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.

Multiyear levels of PCDD/Fs, dl-PCBs and PAHs in background air in central Europe and implications for deposition.

This study presents four years ambient monitoring data of seventeen 2,3,7,8-chlorine substituted polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs), twelve dioxin-like polychlorinated biphenyls (dl-PCBs) and sixteen polycyclic aromatic hydrocarbons (PAHs) designed by the US EPA at a background site in central Europe during 2011-2014. The concentrations expressed as toxic equivalents (TEQs) using the WHO2005-scheme for PCDD/Fs (0.2 fg m-3-61.1 fg m-3) were higher than for dl-PCBs (0.01 fg m-3-2.9 fg m-3), while the opposite was found in terms of mass concentrations. ΣPAHs ranged from 0.20 ng m-3 to 134 ng m-3. The mass concentration profile of PCDD/Fs, dl-PCBs and PAHs was similar throughout the four years. PCDD/Fs and PAHs concentrations were dominated by primary sources peaking in winter, while those of dl-PCBs were controlled by secondary sources characterized by a spring-summer peak. During 2011-2014, no significant decrease in the atmospheric levels of ΣPCDD/Fs was observed. On the other hand, the concentrations of Σdl-PCBs and ΣPAHs were decreasing, with halving times of 5.7 and 2.7 years, respectively. We estimated that 422 pg m-2 year-1-567 pg m-2 year-1 TEQ PCDD/Fs and 3.48 pg m-2 year-1-15.8 pg m-2 year-1 TEQ dl-PCBs were transferred from the air to the ground surfaces via dry particulate deposition during 2011-2014.

Early-life exposure to persistent organic pollutants (OCPs, PBDEs, PCBs, PFASs) and attention-deficit/hyperactivity disorder: A multi-pollutant analysis of a Norwegian birth cohort.

BACKGROUND: Numerous ubiquitous environmental chemicals are established or suspected neurotoxicants, and infants are exposed to a mixture of these during the critical period of brain maturation. However, evidence for associations with the risk of attention-deficit/hyperactivity disorder (ADHD) is sparse. We investigated early-life chemical exposures in relation to ADHD. METHODS: We used a birth cohort of 2606 Norwegian mother-child pairs enrolled 2002-2009 (HUMIS), and studied a subset of 1199 pairs oversampled for child neurodevelopmental outcomes. Concentrations of 27 persistent organic pollutants (14 polychlorinated biphenyls, 5 organochlorine pesticides, 6 brominated flame retardants, and 2 perfluoroalkyl substances) were measured in breast milk, reflecting the child's early-life exposures. We estimated postnatal exposures in the first 2 years of life using a pharmacokinetic model. Fifty-five children had a clinical diagnosis of ADHD (hyperkinetic disorder) by 2016, at a median age of 13 years. We used elastic net penalized logistic regression models to identify associations while adjusting for co-exposure confounding, and subsequently used multivariable logistic regression models to obtain effect estimates for the selected exposures. RESULTS: Breast milk concentrations of perfluorooctane sulfonate (PFOS) and ß­hexachlorocyclohexane (ß-HCH) were associated with increased odds of ADHD: odds ratio (OR) = 1.77, 95% confidence interval (CI): 1.16, 2.72 and OR = 1.75, 95% CI: 1.22, 2.53, per interquartile range increase in ln-transformed concentrations, respectively. Stronger associations were observed among girls than boys for PFOS (pinteraction = 0.025). p,p'­Dichlorodiphenyltrichloroethane (p,p'-DDT) levels were associated with lower odds of ADHD (OR = 0.64, 95% CI: 0.42, 0.97). Hexachlorobenzene (HCB) had a non-linear association with ADHD, with increasing risk in the low-level exposure range that switched to a decreasing risk at concentrations above 8 ng/g lipid. Postnatal exposures showed similar results, whereas effect estimates for other chemicals were weaker and imprecise. CONCLUSIONS: In a multi-pollutant analysis of four classes of chemicals, early-life exposure to ß-HCH and PFOS was associated with increased risk of ADHD, with suggestion of sex-specific effects for PFOS. The unexpected inverse associations between p,p'-DDT and higher HCB levels and ADHD could be due to live birth bias; alternatively, results may be due to chance findings.

Legacy and alternative halogenated flame retardants in human milk in Europe: Implications for children's health.

In this study, 10 polybrominated diphenyl ethers (PBDEs) and 19 alternative halogenated flame retardants (AFRs) were determined in >450 human milk samples across three European countries, representing northern, western and eastern Europe. This study provides first insights into the occurrence of selected AFRs in mother milk samples and compares them among three European countries. Sums of median concentrations of the most frequently detected PBDEs were 2.16, 0.88 and 0.45ngg-1 lipid weight (lw) in Norway, the Netherlands and Slovakia, respectively. The sum of the concentrations of AFRs ranged from 0.14 to 0.25ngg-1lw in all countries, which was 2 to 15 times less compared to Σ7PBDEs. The Penta-BDE replacement, bis(2-ethylhexyl) tetrabromophthalate, BEH-TEBP, was present at the greatest concentrations of any of the AFRs and in some samples exceeded concentrations of BDE 47 and BDE 153. Four AFRs including bromobenzenes (hexabromobenzene, pentabromobenzene, pentabromotoluene) and another Penta-BDE replacement (2-ethylhexyl-2,3,4,5-tetrabromobenzoate, EH-TBB) were detected in >42% of all human milk samples. Because of the potential developmental neurotoxicity of the halogenated flame retardants, infant dietary intakes via breastfeeding were estimated; in four cases the intakes of BDE 47 exceeded the reference dose indicating that the present concentrations may pose a risk for children.

Determination of selected neurotoxic insecticides in small amounts of animal tissue utilizing a newly constructed mini-extractor.

We developed a simple analytical method for the simultaneous determination of representatives of various groups of neurotoxic insecticides (carbaryl, chlorpyrifos, cypermethrin, and α-endosulfan and ß-endosulfan and their metabolite endosulfan sulfate) in limited amounts of animal tissues containing different amounts of lipids. Selected tissues (rodent fat, liver, and brain) were extracted in a special in-house-designed mini-extractor constructed on the basis of the Soxhlet and Twisselmann extractors. A dried tissue sample placed in a small cartridge was extracted, while the nascent extract was simultaneously filtered through a layer of sodium sulfate. The extraction was followed by combined clean-up, including gel permeation chromatography (in case of high lipid content), ultrasonication, and solid-phase extraction chromatography using C18 on silica and aluminum oxide. Gas chromatography coupled with high-resolution mass spectrometry was used for analyte separation, detection, and quantification. Average recoveries for individual insecticides ranged from 82 to 111%. Expanded measurement uncertainties were generally lower than 35%. The developed method was successfully applied to rat tissue samples obtained from an animal model dealing with insecticide exposure during brain development. This method may also be applied to the analytical treatment of small amounts of various types of animal and human tissue samples. A significant advantage achieved using this method is high sample throughput due to the simultaneous treatment of many samples. Graphical abstract Optimized workflow for the determination of selected insecticides in small amounts of animal tissue including newly developed mini-extractor.

An effective clean-up technique for GC/EI-HRMS determination of developmental neurotoxicants in human breast milk.

The increasing number of children suffering from developmental disorders has raised questions regarding their association with the presence of environmental contaminants in mothers and children. We therefore developed a new method for the determination of 78 proven and potential developmental neurotoxicants, including polychlorinated biphenyls, legacy pesticides, pyrethroids, and old and new halogenated flame retardants in breast milk. The essential part of sample preparation was dialysis as a non-destructive clean-up step which was newly used at 10 °C and showed more efficient lipid removal (up to 96%) than the conventional methods such as gel permeation chromatography or freezing-lipid filtration and thus ensured low limits of detection (LOD) by reducing the sample volume prior to injection. Next advantages were significant solvent reduction and no risk of sample cross-contamination. Gas chromatography coupled with high resolution mass spectrometry (GC-HRMS) was subsequently used for the separation and compound quantification. The method was validated using breast milk samples fortified with the analyzed compounds. Recoveries for most of the compounds ranged from 63 to 121% with a relative standard deviation of 2-25%, and LODs ranged between 0.001 and 0.87 ng g-1 lipid weight. The method was applied to breast milk samples from a Dutch birth cohort where 35 out of the 78 compounds were quantified in more than 60% of the samples. For novel flame retardants, the method provides unique results regarding their occurrence in human matrices in Europe. Overall, the analysis of a complex mixture of developmental neurotoxicants could be useful for the assessment of the influence of the studied compounds to child health and development. Graphical abstract Flow diagram of the method and levels of the developmental neurotoxicants in Dutch human milk samples.

Developmental neurotoxicants in human milk: Comparison of levels and intakes in three European countries.

Developmental neurotoxicants (DNTs), such as methylmercury (MeHg), polychlorinated biphenyls (PCBs) and selected organochlorine pesticides (OCPs), have gained increasing interest recently due to their possible relation to developmental disorders in children, which are increasing worldwide. We analyzed levels of 14 developmental neurotoxicants in human milk samples from Slovakia (n=37), the Netherlands (n=120) and Norway (n=388). Positive identification for most target analytes was >95% in all samples. In all three countries MeHg was measured for the first time in mother milk. The highest MeHg levels were observed in Norway (39pgg-1 ww) with the highest fish consumption. Levels of indicator PCBs (iPCBs, sum of PCB 28, 52, 101, 138, 153 and 180), HCB and DDE+DDT were 2-4 times higher in Slovakia compared to the Netherlands or Norway. The levels of MeHg and organochlorine compounds were used for calculations of weekly or daily intakes (top-down approach) by means of pharmacokinetic modeling. The intakes ranged from 0.014 to 0.142µgkgbw-1week-1 for MeHg and from 0.043 to 17.4ngkgbw-1day-1 for organochlorine compounds in all three countries. Intakes of iPCBs exceeded a tolerable daily intake of 10ngkgbw-1day-1 in 16% of the Slovak participants. The top-down estimates were compared with bottom-up intakes based on national dietary estimates and the results showed good consistency between both approaches, with the bottom-up intakes exceeding the top-down by a factor of maximum 3.8 for iPCBs in the Netherlands and 3.9 for HCB in Slovakia. This confirms that food consumption in all three countries represents the dominant pathway of exposure to these developmental neurotoxicants.

Spatiotemporal patterns and potential sources of polychlorinated biphenyl (PCB) contamination in Scots pine (Pinus sylvestris) needles from Europe.

Using pine needles as a bio-sampler of atmospheric contamination is a relatively cheap and easy method, particularly for remote sites. Therefore, pine needles have been used to monitor a range of semi-volatile contaminants in the air. In the present study, pine needles were used to monitor polychlorinated biphenyls (PCBs) in the air at sites with different land use types in Sweden (SW), Czech Republic (CZ), and Slovakia (SK). Spatiotemporal patterns in levels and congener profiles were investigated. Multivariate analysis was used to aid source identification. A comparison was also made between the profile of indicator PCBs (ind-PCBs-PCBs 28, 52, 101, 138, 153, and 180) in pine needles and those in active and passive air samplers. Concentrations in pine needles were 220-5100 ng kg(-1) (∑18PCBs - ind-PCBs and dioxin-like PCBs (dl-PCBs)) and 0.045-1.7 ng toxic equivalent (TEQ) kg(-1) (dry weight (dw)). Thermal sources (e.g., waste incineration) were identified as important sources of PCBs in pine needles. Comparison of profiles in pine needles to active and passive air samplers showed a lesser contribution of lower molecular weight PCBs 28 and 52, as well as a greater contribution of higher molecular weight PCBs (e.g., 180) in pine needles. The dissimilarities in congener profiles were attributed to faster degradation of lower chlorinated congeners from the leaf surface or metabolism by the plant.

Polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and metals in scots pine (Pinus sylvestris) needles from Eastern and Northern Europe: Spatiotemporal patterns, and potential sources.

Pine needles were sampled to determine levels of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and metals in Scots pine (Pinus sylvestris) needles at industrial, urban and background sites in Sweden (SW), Czech Republic (CZ) and Slovakia (SK). Spatial and temporal patterns of PCDD/Fs in pine needles were investigated and principal component analysis (PCA) used to determine spatial patterns, potential sources and transport of PCDD/Fs. Levels of PCDD/Fs in pine needles were generally greatest near to industrial sites (Æ©2,3,7,8-PCDD/Fs (lower bound (LB)): 6 ng kg(-1) - 190 ng kg(-1)) compared to urban and background sites (Æ©2,3,7,8-PCDD/Fs (LB): 0.90 ng kg(-1) - 20 ng kg(-1)). Using metal contamination in pine needles helped to detect spatial patterns and separate local thermal sources of PCDD/Fs.

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.

Characterization of AhR agonists reveals antagonistic activity in European herring gull (Larus argentatus) eggs.

European herring gull (Larus argentatus) eggs from two Norwegian islands, Musvær in the south east and Reiaren in Northern Norway, were screened for dioxins, furans, and dioxin-like and selected non-dioxin-like polychlorinated biphenyls (PCBs), and subjected to non-target analysis to try to identify the aryl hydrocarbon receptor (AhR) agonists, responsible for elevated levels measured using the dioxin responsive chemically activated luciferase expression (DR-CALUX) assay. Eggs from Musvær contained chemically calculated toxic equivalent (WHO TEQ) levels of between 109 and 483 pg TEQ/g lw, and between 82 and 337 pg TEQ/g lw was determined in eggs from Reiaren. In particular PCB126 contributed highly to the total TEQ (69-82%). In 19 of the 23 samples the calculated WHO TEQ was higher than the TEQCALUX. Using CALUX specific relative effect potencies (REPs), the levels were lower at between 77 and 292 pg/g lw in eggs from Musvær and between 55 and 223 pg/g lw in eggs from Reiaren, which was higher than the TEQCALUX in 16 of the 23 samples. However, the means of the REP values and the TEQCALUX were not significantly different. This suggests the presence of compounds that can elicit antagonist effects, with a low binding affinity to the AhR. Non-target analysis identified the presence of hexachlorobenzene (HCB) (quantified at 9.6-185 pg/g lw) but neither this compound nor high concentrations of PCB126 and non-dioxin-like PCBs could explain the differences between the calculated TEQ or REP values and the TEQCALUX. Even though, for most AhR agonists, the sensitivity of herring gulls is not known, the reported levels can be considered to represent a risk for biological effects in the developing embryo, compared to LC50 values in chicken embryos. For human consumers of herring gull eggs, these eggs contain TEQ levels up to four times higher than the maximum tolerable weekly intake.

Influence of titanium dioxide nanoparticles on 2,3,7,8-tetrachlorodibenzo-p-dioxin bioconcentration and toxicity in the marine fish European sea bass (Dicentrarchus labrax).

The present study investigated the influence of nano-TiO(2) (1 mg L(-1)) on 2,3,7,8-tetrachlorodibenzo-p-dioxin(2,3,7,8-TCDD) (46 pg L(-1)) bioconcentration and toxicity in the European sea bass (Dicentrarchus labrax) during 7 days in vivo exposure. A multimarkers approach was applied in different organs: detoxification in liver; innate immunity and pro-inflammatory response and adaptive immunity in gills and spleen; genotoxicity in peripheral erythrocytes and muscle. Bioconcentration of 2,3,7,8-TCDD in presence of nano-TiO2 was investigated in liver, skin and muscle as well as interaction between nano-TiO2 and organic pollutants in artificial sea water (ASW). Nano-TiO2 negatively influenced immune response induced by 2,3,7,8-TCDD in spleen but not in gills and reduced the DNA damage induced by 2,3,7,8-TCDD in erythrocytes. nano-TiO2 did not interfere with 2,3,7,8-TCDD detoxification and bioconcentration according to the observed no interaction of the nano-TiO2 with organic pollutants in ASW.

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.

Interactive effects of n-TiO2 and 2,3,7,8-TCDD on the marine bivalve Mytilus galloprovincialis.

Despite the growing concern over the potential biological impact of nanoparticles (NPs) in the aquatic environment, little is known about their interactions with other pollutants. The bivalve Mytilus sp, largely utilized as a sentinel for marine contamination, has been shown to represent a significant target for different types of NP, including n-TiO2, one of the most widespread in use. In this work, the possible interactive effects of n-TiO2 and 2,3,7,8-TCDD, chosen as models of NP and organic contaminant, respectively, were investigated in Mytilus galloprovincialis. In vitro experiments with n-TiO2 and TCDD, alone and in combination, were carried out in different conditions (concentrations and times of exposure), depending on the target (hemocytes, gill cells and biopsies) and the endpoint measured. Mussels were also exposed in vivo to n-TiO2 (100 µg L(-1)) or to TCDD (0.25 µg L(-1)), alone and in combination, for 96 h. A wide range of biomarkers, from molecular to tissue level, were measured: lysosomal membrane stability and phagocytosis in hemocytes, ATP-binding cassette efflux transporters in gills (gene transcription and efflux activity), several biomarkers of genotoxicity in gill and digestive cells (DNA damage, random amplified polymorphic DNA-RAPD changes), lysosomal biomarkers and transcription of selected genes in the digestive gland. The results demonstrate that n-TiO2 and TCDD can exert synergistic or antagonistic effects, depending on experimental condition, cell/tissue and type of measured response. Some of these interactions may result from a significant increase in TCDD accumulation in whole mussel organisms in the presence of n-TiO2, indicating a Trojan horse effect. The results represent the most extensive data obtained so far on the sub-lethal effects of NPs and organic contaminants in aquatic organisms. Moreover, these data extend the knowledge on the molecular and cellular targets of NPs in bivalves.

Toxicokinetic modeling of persistent organic pollutant levels in blood from birth to 45 months of age in longitudinal birth cohort studies.

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.

PCDDs, PCDFs, dioxin-like PCBs and indicator PCBs in soil from five selected areas in Slovakia.

There is a lack of information regarding persistent organic pollutants (POPs) in soil from Slovakia. This paper reports the concentrations of 17 polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), 12 dioxin-like polychlorinated biphenyls (dl-PCBs) and 6 indicator PCBs associated with 32 soil samples collected in 2007 from areas in the vicinity up to several kilometres from four selected industrial PCDD/F sources in Slovakia and one background area. The results show that the total WHO(1998)-PCDD/F/dl-PCB-TEQ concentrations varied from 0.34 to 18.05 pg g(-1) dry weight (dw) and the average total TEQ concentrations in samples collected at the Sala, Kosice, Krompachy and Dubová areas were 3.18, 2.64, 7.80, and 3.19 pg g(-1)dw respectively. The average of the total WHO(1998)-TEQ values in three soil samples representing the background Starina area was 0.66 pg g(-1) dw. The predominant contaminants among 2,3,7,8-substituted PCDD/Fs, dl-PCB, and indicator PCBs was OCDD, PCB 118, and PCB 153 respectively. The major contributors to the TEQ were 2,3,4,7,8-PeCDF, PCB 126, 1,2,3,7,8-PeCDD, PCB 156 and 1,2,3,4,7,8-HxCDF+1,2,3,4,7,9-HxCDF in descending order.

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.

Assessment of exposure to PCB 153 from breast feeding and normal food intake in individual children using a system approach model.

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<0.001) as well as with duration of breast feeding (r=0.64, p<0.001). It makes possible to determine each subject's exposure profile expressed as AUC of PCBs serum concentration with a minimum model parameters. PCB body burden in most infants was strongly associated with duration of breast feeding in most, but not all children, was apparent from model output.

PCDD, PCDF, PCB and PBDE concentrations in breast milk of mothers residing in selected areas of Slovakia.

The concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), dioxin-like polychlorinated biphenyls (dl-PCBs) and polybrominated diphenylethers (PBDEs) in 33 breast milk samples collected in 2006-2007 from primipara mothers close to four industrial areas of Slovak Republic were determined. The total PCDDs/PCDFs and dl-PCBs expressed as TEQ based on WHO TEFs 1998 in breast milk samples varied from 5.0 to 51.8 pg g(-1) fat (median: 13.1 pg g(-1) fat; mean: 18.0 pg g(-1) fat). The measurements of seven PBDE congeners (IUPAC No. 28, 47, 99, 100, 153, 154, and 183) were performed for the first time in human milk from Slovakia. PBDE levels ranged between 0.22 and 1.62 ng g(-1) fat, with median and mean value of 0.43 ng g(-1) fat and 0.57 ng g(-1) fat respectively. No statistically significant differences were observed between studied areas in total PBDE concentrations. Furthermore, this study presents first results concerning the daily intake (DI) of PCDDs/PCDFs and dioxin-like compounds for the most vulnerable breast-fed infant population in Slovakia. The total PCDD/PCDF and dl-PCB DI for an infant during the first 2 months of life was estimated in a range from 14.4 to 230 pg TEQ kg(-1)b.w., with a median value of 58.9 pg TEQ kg(-1)b.w.. The DI values substantially exceeded the tolerable daily intake (TDI) 1-4 pg TEQ kg(-1)b.w. recommended by WHO. The dietary infant intake concerning PBDEs was estimated to be between 0.69 and 7.1 ng kg(-1)b.w.d(-1), with median value of 1.7 ng kg(-1)b.w.d(-1).