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The impacts of single-nucleotide polymorphisms (SNPs) in ALAD and VDR genes on Pb health effects and/or kinetics are inconclusive at low exposure levels, while studies including APOE SNPs are rare. In this study, we examined the associations of ALAD, VDR and APOE SNPs with exposure biomarkers of Pb and other trace elements (TEs) in Italian pregnant women (N = 873, aged 18-44 years) and their newborns (N = 619) with low-level mixed-element exposure through diet, the environment or endogenously. DNA from maternal peripheral venous blood (mB), sampled during the second and third trimesters, was genotyped for ALAD (rs1800435, rs1805313, rs1139488, rs818708), VDR (rs2228570, rs1544410, rs7975232, rs731236) and APOE (rs429358, rs7421) using TaqMan SNP assays. Personal and lifestyle data and TE levels (mB, maternal plasma, hair and mixed umbilical cord blood [CB]) from the PHIME project were used. Multiple linear regression models, controlling for confounding variables, were performed to test the associations between SNPs and TEs. The geometric means of mB-Pb, mB-Hg, mB-As and mB-Cd (11.0 ng/g, 2.16 ng/g, 1.38 ng/g and 0.31 ng/g, respectively) indicated low exposure levels, whereas maternal plasma Zn and Se (0.72 μg/mL and 78.6 ng/g, respectively) indicated adequate micronutritional status. Variant alleles of ALAD rs1800435 and rs1805313 were negatively associated with mB-Pb levels, whereas a positive association was observed for rs1139488. None of the VDR SNPs or their haplotypes had any association with Pb levels. Regarding APOE, the ɛ4 allele was associated with lower mB-Hg and CB-Hg, while a positive association was found with the ɛ2 allele and CB-Pb when the model included only newborn girls. The observed associations indicate possible modification effects of ALAD and APOE SNPs on Pb or Hg kinetics in women and their newborns with low exposure to non-essential TEs, as well as an adequate nutritional status of Zn and Se.

Single nucleotide polymorphisms (SNPs) of cytochrome P450 (CYPs) and UDP-glucuronosyltransferase (UGTs) genes have been proposed to influence phthalates and 1,2-cyclo-hexanedicarboxylic acid diisononyl ester (DINCH) biotransformation but have not been investigated on a populational level. We investigated the role of SNPs in CYP2C9, CYP2C19, CYP2D6, UGT2B15, and UGT1A7 genes in the biotransformation of phthalates (DEHP, DEP, DiBP, DnBP, BBzP, DiNP, DidP) and DINCH by determining their urine metabolites. From the Slovenian study population of 274 men and 289 lactating primiparous women we obtained data on phthalate and DINCH urine metabolite levels (MEHP, 5OH-MEHP, 5oxo-MEHP, 5cx-MEPP, MEP, MiBP, MnBP, MBzP, cx-MINP, OH-MiDP, MCHP, MnPeP, MnOP, 5OH-MINCH, 5oxo-MINCH), SNP genotypes (rs1057910 = CYP2C9*3, rs1799853 = CYP2C9*2, rs4244285 = CYP2C19*2, rs12248560 = CYP2C19*17, rs3892097 = CYP2D6*4, rs1902023 = UGT2B15*2, and rs11692021 = UGT1A7*3) and questionnaires. Associations of SNPs with levels of metabolites and their ratios were assessed by multiple linear regression and ordinary logistic regression analyses. Significant associations were observed for CYP2C9*2, CYP2C9*3, CYP2C19*17, and UGT1A7*3 SNPs. The most pronounced was the influence of CYP2C9*2 and *3 on the reduced DEHP biotransformation, with lower levels of metabolites and their ratios in men and women. In contrast, carriers of CYP2C19*17 showed higher urine levels of DEHP metabolites in both genders, and in women also in higher DiNP, DiDP, and DINCH metabolite levels. The presence of UGT1A7*3 was associated with increased metabolite levels of DINCH in men and of DiBP and DBzP in women. Statistical models explained up to 27% of variability in metabolite levels or their ratios. Our observations confirm the effect of CYP2C9*2 and *3 SNPs towards reduced DEHP biotransformation. We show that CYP2C9*2, CYP2C9*3, CYP2C19*17, and UGT1A7*3 SNPs might represent biomarkers of susceptibility or resilience in phthalates and DINCH exposure that have been so far unrecognised.

In the Arctic, main sources of persistent organic pollutants and potentially toxic elements are industry and agriculture in the lower latitudes. However, there are also local sources of pollution. Our study was focused on possible pollution in the Finnish Lapland, transferred from the Pechenganikel industrial complex located in the borders of Russia, Finland and Norway. Local food items and blood samples of pregnant women from the Inari municipality were collected and organochlorine compounds (OCs) and metal(oid)s analyzed. Most of the examined food samples showed detectable levels of these compounds. The mean concentrations of DDTs and polychlorobiphenyls (PCBs) were higher in fish (0.18-0.32 ng/g and 0.34-0.64 ng/g, respectively), than in the other food groups (0.027-0.047 ng/g and 0.11-0.20 ng/g, respectively). PCBs were found at the highest concentrations in blood samples of the pregnant women, and congeners 153 and 118 were dominant. The mean concentration of PCB153, 0.29 μg/kg serum lipid, was lower than those described in many other studies. Concerning DDTs, the 4,4'-DDT/4,4'-DDE ratio, 0.092, in the blood samples was lower than that observed in the food items, 0.25-0.71, reflecting old uses of the DDT pesticide. None of the observed levels of selected potentially toxic elements in blood samples and in food items exceeded the known safe limits. Higher concentrations of PCB52 and γ-HCH were observed in the serum of pregnant women who consumed greater amounts of meat, and berries and mushrooms, respectively. The OC concentrations from the pregnant women currently studied were lower than those observed fourteen years ago with pregnant women from the same municipality. Compounds whose occurrence is likely related to a long-distance transport showed clear decreases, e.g., 63% for PCBs, and for those from pesticides, decreases were 93% and 97% for 4,4'-DDE and β-HCH, respectively. No obvious influence from the Pechenganikel complex is observed from the results., The research leading to these results has received funding from the Kolarctic ENPI CBC 2007–2013 Program project “Food and Health Security in the Norwegian, Russian and Finnish border regions: linking local industries, communities and socio-economic impacts”, European Community's Seventh Framework Program FP7/2007–2013—Environment (including Climate Change) FP7-ENV-2008-1—under Grant Agreement No: 226534- ArcRisk and Horizon 2020 project: EDC-MET (H2020-HEALTH/0490–825762). The financial support of the Slovenian research agency ARRS through a program P1-0143 is acknowledged.

The current study aims to characterize exposure and risk associated to bisphenol-A (BPA) exposure in Slovenia, starting from biomonitoring data. Based on the urinary data, daily intake for the individuals was back-calculated using a physiology based biokinetic (PBBK) model properly parameterized for BPA, coupled with an exposure reconstruction algorithm. Re-running the PBBK model in forward mode allowed the estimation of biologically effective dose (free plasma BPA) and the respective daily area under the curve (AUC). Finally, risk characterization ratio was derived using both external and internal dose metrics. The urinary BPA levels were found low, with GM of 0.79, 1.51 and 0.20 μg/g creatinine for mothers, children and fathers respectively, similar to the levels of other European countries. Based on the above and accounting for the dynamics of exposure and biokinetics, daily intake was estimated, median exposure levels have been estimated equal to 0.019, 0.035 and 0.005 μg/kg_bw/d for mothers, fathers and children respectively. The highest estimated intake level was found in a child, equal to 0.87 μg/kg_bw/d, while the maximum intake for mothers and fathers were 0.7 and 0.8 μg/ kg_bw/d respectively. The respective RCR levels using the EFSA t-TDI of 4 μg/kg_bw/d were 2 magnitudes of order lower below 1, independently of the selected method. It has to be noted that had daily intake been estimated solely based on the urinary concentrations mass balance, the estimated intake would be lower, as a result of the oversimplification on exposure and elimination time dynamics. This highlights the importance for using PBBK modelling based exposure reconstruction schemes for rapidly metabolized and excreted compounds such as BPA, as well as the study design of efficient sampling for rapidly metabolized compounds.

Chemicals such as bisphenols, parabens and triclosan are endocrine disrupting chemicals. They are used in a wide variety of consumer products, making human exposure to those chemicals widespread. In the present study, levels of three bisphenols (bisphenol A, F and S), 7 parabens (methyl-, ethyl-, isopropyl-, propyl-, isobutyl-, butyl-, benzyl paraben) and triclosan were measured in first morning void from 246 Slovenian children and adolescents, aged 6-9 and 11-15 years and living in a rural region of Slovenia. Median levels of specific-gravity corrected levels for bisphenol A, bisphenol F, methyl paraben and ethyl paraben were 1.9, 0.085, 5.4 and 2.5 µg/L for children and 1.6, 0.11, 7.2 and 6.0 µg/L for adolescents, respectively. Median levels for all other endocrine disrupting chemicals were < LOQ. The levels are comparable with the levels reported in studies across the world. Exposure was age, sex, and location specific. Higher levels of bisphenol F and ethyl paraben were found in the samples of adolescents, while higher levels of methyl paraben were found in samples from girls. Furthermore, individuals living in one of the sampling locations, Goricko, were exposed to higher levels of bisphenol F and ethyl paraben than those in the remaining two sampling locations. Information about participants' dietary habits, use of food packaging and personal care products was obtained through questionnaires, and used to investigate associations between urinary levels of the biomarkers and potential exposure sources. High fat foods were associated with bisphenol A exposure, and cosmetics items such as lipstick and perfume with methyl paraben exposure. Significant correlation between methyl- and propyl paraben was observed in children's samples, suggesting similar exposure sources, while other compounds were not largely correlated, indicating independent sources. Furthermore, association between a single nucleotide polymorphism (SNP) in UGT2B15 gene and urinary levels of methyl and ethyl paraben was observed, showing the role of UGT2B15 isoform in methyl and ethyl paraben metabolism as well as indicating the SNP rs1902023 as a potential biomarker of susceptibility to adverse effects caused by the exposure. The present study reports exposure of children and adolescents in Slovenia to a wide range of different endocrine disrupting chemicals for the first time, connecting it to exposure patterns and exposure sources. The study is to the authors' knowledge the first that investigates direct connection between levels of urinary endocrine disrupting chemical biomarkers and genetic polymorphism in UGT2B15.

There are extensive data on the toxicity of glyphosate (GLY) based herbicides (GBH), however the interpretation of some data (e.g. carcinogenic effect) are subject to controversy. For the appropriate health risk assessment more data on exposure levels in the general population, especially in susceptible groups such as pregnant women, the elderly and children are needed. The aims of the present study were to estimate the exposure to GLY and its major metabolite aminomethylphosphonic acid (AMPA) in children and adolescents living in agricultural areas, to identify possible determinants of the exposure, and to assess co-exposure with elements. In total, 149 children (aged 7–10 years, 55% girls) and 97 adolescents (aged 12–15 years; 44% girls) were recruited in 2018 from rural areas of Northeastern Slovenia. The effect of seasonal GLY application on the exposure was estimated using GLY and AMPA levels determined by GC–MS/MS in first morning urine in winter (n = 246) and in late-spring/early-summer seasons (n = 225). Levels of elements were determined by ICP-MS in urine in both samplings and in blood or plasma in the first sampling. Questionnaire data on basic characteristics, dietary habits, living environments and use of pesticides were obtained for all participants. GLY and AMPA were detected in 27% and 50% of urine samples from the first sampling period, respectively; and in 22% and 56% from the second sampling period, respectively. Geometric means and medians of both AMPA and GLY were below or at the limit of quantification (≤LOQ; 0.1 µg/L). Children rather than adolescents tended to have higher exposure, as did, boys rather than girls among adolescents. The exposure did not significantly differ between both sampling periods. Except for one individual, exposure was not higher among participants who reported use of GLY or herbicides in the vicinity of child’s home or live in close vicinity of agriculture, orchards, vineyards, gardens, sport courts or cemeteries. The extensive food consumption frequency data revealed higher exposure to GLY and AMPA only among individuals with higher consumption of nuts and wholegrain rice. Levels of AMPA and GLY were significantly positively correlated, with considerably stronger correlation in urine of the second than the first sampling (Spearman’s rank coefficient: 0.49 vs 0.22, respectively). Urine levels of As, Pb, Co, Zn and Cu were significantly higher in participants with GLY and/or AMPA levels ≥LOQ than with levels In conclusion, this first estimation of GLY and AMPA exposure in a Slovenian study population showed much lower levels when compared to levels reported in similar studies worldwide. Some results might be explained by more intensive use of GBH in spring, but in general we were unable to distinguish between exposure from the diet or use of GBH in residential environments.

In the present study, urinary bisphenol A (BPA) levels were reported for the first time in the Slovenian general population and were evaluated with regard to dietary and non-dietary exposure sources, and compared according to age, gender and area of residence. First morning urine was collected from children (6–11 years), their mothers (30–52 years) and fathers (30–53 years), living in urban and rural areas of Slovenia. Besides basic questionnaire data on general population characteristics, socio-economic status and dietary habits, BPA-specific data was also collected, including consumption of food and beverages from plastic and canned containers, presence of white dental fillings, the use of specific consumer products and hormonal treatments. Urine samples were analysed for both free and conjugated BPA using GC-MS/MS. The urinary levels of total BPA in children, mothers and fathers were low, with geometric means of 1.51, 0.79, and 0.20 μg/g creatinine, respectively. The levels were comparable with the levels reported for other European countries and were all below the current health-based guidance values. In line with large-scale surveys, the data revealed age-dependant BPA urinary levels, with the highest levels in the youngest age group. In mothers, urinary levels of BPA were determined by hormonal interactions more than dietary sources, while a positive association between urinary BPA and diet was apparent in children (canned food/drink and food from plastic material) and fathers (canned food/drink). The study clearly shows that physiological and behavioural differences account for differences in levels of urinary BPA among study groups, a finding that sets the priorities for future research.

Pt nanoparticles (NPs) are directly emitted into air from human activities, contributing to the pollutant load of plants and posing risks to food safety. Foliar surface characteristics affect particle interception and retention from air; however the influence of foliar surface free energy (SFE), a quantitative measure of polar and dispersive surface forces which determine hydrophobicity/hydrophilicity, has not been investigated. Here, soil-grown plantlet leaves of arugula (low SFE) and escarole (high SFE) were exposed to Pt NPs (5–500 mg Pt NPs per L) for 5 days. Pt NP internalization and translocation, aggregation/agglomeration on leaf surfaces, and SFE changes were analyzed. Plantlets were also root-exposed to Pt NPs (one exposure to 20 mL of 50 mg L−1 dispersion) to provide a comparison between leaf-to-root and root-to-leaf translocation. Among foliar-exposed plants, inductively coupled plasma-mass spectrometry data showed that relative to escarole, arugula contained higher Pt concentrations in leaves (33, 31, and 14 times higher for 5, 50, and 500 mg L−1 exposures, respectively) and lower Pt concentrations in roots (6, 4, and 3 times lower for 5, 50, and 500 mg L−1 exposures, respectively). For both plants, the proportion of Pt translocated from roots to leaves (99% and 28% for arugula and escarole, respectively) was higher than that from leaves to roots (

Metal(loid)s' accumulation and interactions were studied in Tetrahymena thermophila after 24 h exposure to 100 µM CuI, 20 µM CdII, 1 µM of AgI, HgII, PbII, AsIII, AsV, SbIII, SbV, SeIV, or ...

Characterization of the exposome, the totality of all environmental factors that one is exposed to from conception onwards, has been recommended to better evaluate the role of environmental influences on developmental programming and life- course vulnerability to major chronic diseases. In the framework of the Health and Environment- wide Associations based on Large population Surveys (HEALS) project we considered the pregnancy exposome exploiting two databases (PRIME and REPRO PL) that include birth cohorts from three EU countries (Croatia, Slovenia and Poland). The databases contained information on several chemical exposures, socio-demographic, lifestyle and health related factors from conception to child birth, and neuropsychological scores assessed by the Bayley Scales of Infant and Toddler Development in the first two years of life. Our main goal was to assess consistency of environmental influences on neurodevelopment, if any, across European countries differing for geographical, socio-demographic characteristics and levels of chemical exposures to metals such as lead (Pb), mercury (Hg), cadmium (Cd) and trace elements, including micronutrients such as zinc (Zn) and selenium (Se). To this aim, we first selected variables common to the different databases, then applied univariate and multivariate regression analyses to identify factors linked to neurodevelopment, and finally performed meta-analysis to detect potential heterogeneity among cohorts and pooled estimates. Significant differences in exposure levels among the three sub-cohorts were observed as for Hg and Se ; exposure levels under study were relatively low and within the range described in existing EU biomonitoring studies. The univariate analyses did not show any common pattern of association as only in the Polish cohort chemical exposure had an impact on neuropsychological outcome. In the meta-analysis, some consistent trends were evident, relative to the adverse influence of Pb on children's language and cognition and the positive influence of Se on language abilities. The effects of the neurotoxic metal Hg positively influenced the motor scores in the Polish cohorts, while it decreased the motor scores in the Slovenia and Croatian sub-cohorts. The only socio-demographic factor consistently associated to the outcome among cohorts was child's sex, with females performing better than males on cognitive and language scores. These findings point to the need of harmonizing existing cohorts or creating prospective study designs that facilitate comparisons in the exposome over time, places and kind of environmental exposures.

The maternal diet and living environment can affect levels of chemical elements and fatty acid (FA) composition and their stable isotopes (δ13CFA) in human milk. Information obtained from questionnaires is frequently imprecise, thus limiting proper associations between external and internal exposures as well as health effects. In this study, we focused on seafood as a source of potentially toxic and essential elements and nutritional FAs. Concentrations of selected elements in human milk (As, Cd, Cu, Mn, Pb, Se and Zn) were determined using inductively coupled plasma mass spectrometry (ICP-MS) and Hg using cold vapour atomic-absorption spectrometry (CV-AAS). The identification and quantification of FAs in maternal milk were performed by an in-situ trans-esterification method (FAMEs), and the characterization of FAMEs was performed by gas chromatography with a flame ionisation detector (GC-FID). δ13CFA was determined by gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). Seventy-four lactating Slovenian women from the coastal area of Koper (KP), with more frequent consumption of seafood, and the inland area of Pomurje (MS), with less frequent seafood consumption, were included in this study. Along with basic statistical analyses, data mining approaches (classification and clustering) were applied to investigate whether FA composition and δ13CFA could improve the information regarding dietary sources of potentially toxic elements. As and Hg levels in milk were found to be statistically higher in populations from KP than in those from MS, and 71% of individual FAs and 30% of individual δ13CFA values in milk differed statistically between the studied areas. In 19 cases, the levels of FAs in milk were higher in KP than in MS; these FAs include C20:5ω3 and C22:6ω3/C24:1ω9, which are typically contained in fish. In 16 cases, the mean percentage of FAs was higher in MS than in KP; these FAs include the PUFAs C18:2ω6, C18:3ω3, and C20:4ω6 which are important for human and infant growth. The difference in δ13C levels of C10:0, C12:0, C14:0, C16:1, C16:0, C18:1ω9c, C22:6ω3, and δ13C 18:0-16:0 in the study groups was statistically significant. In all seven cases where δ13C of FA significantly differed between KP and MS, δ13C was higher in KP, indicating a higher proportion of a marine-based diet. The data mining approaches confirmed that the percentage of selected FAs (iC17:0, C4:0, C18:2ω6t, aC17:0, CLA, and C22:4ω6) and δ13CFA of C18:1ω9c in human milk could be used to distinguish between high and low frequency of fresh seafood consumption.

Persistent organic pollutants (POPs) represent a concern for the environment and human health due to their persistence and toxicity. Exposure in Slovenia is geographically differentiated because the country, as part of former Yugoslavia, has a history of industry and regional contamination and is – at the same time – known for its clean nature. The PCB pollution of the Krupa River drew the public’s attention to the chemical burden of Slovenians, and the demand for studies has been rising since. We assessed the exposure of men (n = 548) and primiparous women (n = 536) to POPs in 12 regions of Slovenia as well as exposure pathways via questionnaires. Most PCDD/Fs, PCBs, and PBDEs could be determined in pooled samples of maternal milk at low concentrations (1.57 pg/gTEQ, 1.47 pg/gTEQ, and 1076 pg/g fat, respectively), but a much lower number of compounds could be measured above the LOQ in pooled men’s plasma samples (PCDD/Fs 0.08 pg/gTEQ, PCBs 0.007 pg/gTEQ, ΣPBDE 920 pg/g), and only HCB, p,p’-DDE, ΣDDT, and the non-dioxin-like PCB congeners 138, 153, and 180 could be determined in individual samples of milk (concentration range 5–60 ng/g fat). In individual samples of men’s serum, only p,p’-DDE and ΣPCB were detected at concentrations of 0.25 ng/g and 0.3 ng/g, respectively. Nonetheless, we were able to differentiate between polluted and unpolluted areas on a national level, with higher exposure levels in the PCB polluted region of Bela Krajina, the industrial region Zasavje, and the capital, Ljubljana. Despite low concentrations, determinants of exposure, such as age, proximity to roads, old building materials, private water supplies, and consumption of alcohol, fish, meat, and eggs that have previously been observed only at higher levels could still be identified. Furthermore, levels of PCBs and PBDEs were highly correlated suggesting common exposure sources and pathways, whereas PCDD/Fs were correlated to a lesser extent. The calculated ratio between DDT and DDE in maternal milk samples was decreasing with the year of sampling, suggesting no ongoing exposure to DDT. The study findings suggest low exposure of men and lactating women to legacy pollutants in Slovenia, which gave rise to the hypothesis that Slovenia’s geographical location might provide shelter from the long-range transport of POPs via Westerly winds. This hypothesis remains to be confirmed within future studies.

500 years of mercury (Hg) mining in the town of Idrija has caused severe pollution in Idrija and its surroundings. Following the closure of the mine in 1995, the environment remains contaminated with Hg. Sources of elemental-, inorganic- and methyl Hg exposure were identified, potential environmental level of exposure to Hg was evaluated and actual internal exposure to Hg was assessed in selected susceptible population groups comprising school-age children and pregnant women living in Idrija and in control groups from rural and urban environments. The study of pregnant women (n=31) was conducted between 2003 and 2008, and the study of school-age children (n=176) in 2008. Potential interaction of Hg with selenium (Se) in plasma was assessed in both study populations, while in pregnant women antioxidative enzyme activity (glutathione peroxidase, superoxide dismutase and catalase) in erythrocytes of maternal and cord blood was also assessed. Actual exposure to Hg as indicated by levels of Hg in children's blood (geometric mean (GM) 0.92µg/L), mother's blood (GM 1.86µg/L), children's urine (GM 1.08µg/g crea.), mother's urine (GM 2.51µg/L), children's hair (GM 241ng/g) and mother's hair (GM 251ng/g) was higher in the two study groups from Idrija than in the control groups from rural areas, but was still at the level of a "normal" population and reflects mainly exposure to elemental Hg (Hg°) from dental amalgam and, to a certain extent atmospheric Hg°. Furthermore, the internal doses of Hg received during pregnancy did not decrease the bioavailability of Se. Based on observation in children, the increase in Se protein expression is suggested to be a consequence of moderately elevated exposure to Hg°. The observed changes in activity of antioxidative enzymes, as biomarkers of oxidative stress, appear to be mainly associated with pregnancy per se and not with an increased exposure to Hg. In view of the continuing increased potential for Hg exposure and the low number of pregnant women studied, the results warrant a further longitudinal study of a larger group of pregnant women residing in the area of the former mercury mine.

Urine cadmium (Cd) and renal function biomarkers, mostly analysed in urine spot samples, are well established biomarkers of occupational exposure. Their use and associations at low environmental level are common, but have recently been questioned, particularly in terms of physiological variability and normalisation bias in the case of urine spot samples.To determine the appropriateness of spot urine and/or blood Cd exposure biomarkers and their relationships with renal function biomarkers at low levels of exposure. To this end, we used data from Slovenian human biomonitoring program involving 1081 Slovenians (548 males, mean age 31 years; 533 lactating females, mean age 29 years; 2007-2015) who have not been exposed to Cd occupationally.Geometric means (GMs) of Cd in blood and spot urine samples were 0.27ng/mL (0.28 for males and 0.33 for females) and 0.19ng/mL (0.21 for males and 0.17 for females), respectively. Differing results were obtained when contrasting normalisation by urine creatinine with specific gravity. GMs of urine albumin (Alb), alpha-1-microglobulin (A1M), N-acetyl-beta-glucosaminidase (NAG), and immunoglobulin G (IgG) were far below their upper reference limits. Statistical analysis of unnormalised or normalised urine data often yielded inconsistent and conflicting results (or trends), so association analyses with unnormalised data were taken as more valid. Relatively weak positive associations were observed between urine Cd (ng/mL) and blood Cd (β=0.11, p=0.002 for males and β=0.33, p0.001 for females) and for females between urine NAG and blood Cd (β=0.14, p=0.04). No associations were found between other renal function biomarkers and blood Cd. Associations between Cd and renal function biomarkers in urine were stronger (p0.05, β=0.11-0.63). Mostly, all of the associations stayed significant but weakened after normalisation for diuresis. In the case of A1M, its associations with Cd were influenced by current smoking and blood Pb in males and by pre-pregnancy smoking and blood Se in females (β up to 0.34, p0.001). Statistical analysis of unnormalised or normalised urine data often yielded inconsistent and conflicting results (or trends), so association analyses data with unnormalised were taken as more valid.The observed uncertainties introduced by urine normalisation, particularly by creatinine, confirm blood Cd as a superior low-Cd exposure biomarker versus urine Cd in cases when 24h urine is unattainable. Evidence that A1M can be positively related to Cd, smoking (current or pre-pregnancy), Pb, and Se status, points to the versatile biological functions of A1M.

Phthalates are widespread contaminants with differing chemical characteristics, which largely determine their product applications, and they can leach into the environment. Due to their endocrine disruptive properties at long-term low-level exposure, they propose a health threat to people that has been associated with several adverse health effects such as: decreased male fertility and impacts on neurological development. People are exposed to different phthalates on a daily basis. Accordingly, this study aims to determine urinary concentrations of seven phthalate metabolites in Slovenian mothers (n = 155), fathers (n =77), and children (n =155) within the European project DEMOCOPHES and to identify potential sources of exposure using questionnaire data on sociodemographic characteristics. Furthermore, the appropriateness of two adjustment methods (creatinine and specific gravity) has been evaluated. First morning urine samples were obtained from one urban and one rural location in 2011. Samples were analysed with Ultra Performance Liquid Chromatography Tandem Mass Spectrometry according to the COPHES SOP protocol by VITO NV laboratory in Belgium. All investigated metabolites were detected in all populations. Children's urinary concentrations exceeded those of adults for most metabolites. We observed variations in concentrations depending on sociodemographic and geographic characteristics, such as food and product sources (e.g. plastic packaging, tins, personal care products, PVC) as well as lifestyle and habits (e.g. living space, time spent outside). We observed geographic and sociodemographic differences in our populations that could be confirmed for the three populations separately and for family units. Concentrations are significantly higher at the rural sampling location as well as in households with a lower level of education. We found both the urinary concentrations and the intake doses to be within the European range as presented in the literature. Between creatinine and specific gravity, we found specific gravity the more appropriate option for phthalates. To our knowledge, this is the first study investigating exposure to phthalates in the Slovenian population while considering the common exposure of family units.

Objectives The aim of this study was to evaluate the association of maternal blood selenium (Se) levels and cord blood Se levels with neonatal cerebellum measures and child neurodevelopment at the age of 18 months. Moreover, to investigate whether the neonatal cerebellum measures could be used as a potential biomarker for selenium homeostasis during pregnancy. Study group and methods The study population consisted of 205 mother-child pairs from Croatian Mother and Child Cohort. Maternal blood and cord blood were obtained at delivery and selenium level was analyzed by Inductively Coupled Plasma Mass Spectrometry. Cranial ultrasonography examination was performed on 49 newborns – cerebellum length and width have been measured. Neurodevelopmental assessment of cognitive, language and motor skills were conducted on 154 children, using The Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), at the age of 18 months. Results The mean levels of selenium in maternal blood and cord blood were 92.6 ng/g and 97.0 ng/g, respectively. Maternal blood selenium levels were moderately and negatively correlated (r = −0.372; p = 0.008) with cerebellum length, while cord blood selenium levels were positively correlated with cerebellum width (r = 0.613; p = 0.007) among female children group. Maternal blood selenium levels were weakly and positively correlated (r = 0.176; p = 0.029) with child's cognitive abilities. Conclusion To the best of our knowledge, our study is the first one investigating the association between neonatal brain measures and selenium levels in mother-child pairs. Our results indicate that prenatal selenium intake correlated with cerebellum length and width measured by cranial ultrasonography. Hence, cerebellum may be used as a potential biomarker and a target “organ” for early detection of possible adverse effects of prenatal status to various micronutrients.

The relationships between inorganic arsenic (iAs) metabolism, selenium (Se) status, and genetic polymorphisms of various genes, commonly studied in populations exposed to high levels of iAs from drinking water, were studied in a Croatian- Slovenian population from the wider PHIME-CROME project. Population consisted of 136 pregnant women in the 3rd trimester and 176 non-pregnant women with their children (n = 176, 8–9 years old). Their exposure to iAs, defined by As (speciation) analyses of biological samples, was low. The sums of biologically active metabolites (arsenite + arsenate + methylated As forms) for pregnant women, non-pregnant women, and children, respectively were: 3.23 (2.84–3.68), 1.83 (1.54– 2.16) and 2.18 (1.86–2.54) ng/mLSG ; GM (95 CI). Corresponding plasma Se levels were: 54.8 (52.8– 56.9), 82.3 (80.4–84.0) and 65.8 (64.3–67.3) ng/mL ; GM (95 CI). As methylation efficiency indexes confirmed the relationship between pregnancy/childhood and better methylation efficiency. Archived blood and/or saliva samples were used for single nucleotide polymorphism (SNP) genotyping of arsenic(3+) methyltransferase - AS3MT (rs7085104, rs3740400, rs3740393, rs3740390, rs11191439, rs10748835, rs1046778 and the corresponding AS3MT haplotype) ; methylene tetrahydrofolate reductase - MTHFR (rs1801131, rs1801133) ; aquaporin - AQP 4 and 9 (rs9951307 and rs2414539) ; selenoprotein P1 - SELENOP (rs7579, rs3877899) ; indolethylamine N- methyltransferase - INMT (rs6970396) ; and metallothionein 2A - MT2A (rs28366003). Associations of SNPs with As parameters and urine Se were determined through multiple regression analyses adjusted using appropriate confounders (blood As, plasma Se, ever smoking, etc.). SNPs’ influence on As methylation, defined particularly by the secondary methylation index (SMI), confirmed the ‘protective’ role of minor alleles of six AS3MT SNPs and their haplotype only among non-pregnant women. Among the other investigated genes, the carriers of AQP9 (rs2414539) were associated with more efficient As methylation and higher urine concentration of As and Se among non-pregnant women ; poorer methylation was observed for carriers of AQP4 (rs9951307) among pregnant women and SELENOP (rs7579) among non- pregnant women ; MT2A (rs28366003) was associated with higher urine concentration of AsIII regardless of the pregnancy status ; and INMT (rs6970396) was associated with higher As and Se concentration in non-pregnant women. Among confounders, the strongest influence was observed for plasma Se ; it reduced urine AsIII concentration during pregnancy and increased secondary methylation index among non-pregnant women. In the present study of populations with low As exposure, we observed a few new As–gene associations (particularly with AQPs). More reliable interpretations will be possible after their confirmation in larger populations with higher As exposure levels.

The European Union's 7th Framework Programme (EU's FP7) project HEALS - Health and Environment-wide Associations based on Large Population Surveys - aims a refinement of the methodology to elucidate the human exposome. Human biomonitoring (HBM) provides a valuable tool for understanding the magnitude of human exposure from all pathways and sources. However, availability of specific biomarkers of exposure (BoE) is limited. The objective was to summarize the availability of BoEs for a broad range of environmental stressors and exposure determinants and corresponding reference and exposure limit values and biomonitoring equivalents useful for unraveling the exposome using the framework of environment-wide association studies (EWAS). In a face-to-face group discussion, scope, content, and structure of the HEALS deliverable "Guidelines for appropriate BoE selection for EWAS studies" were determined. An expert-driven, distributed, narrative review process involving around 30 individuals of the HEALS consortium made it possible to include extensive information targeted towards the specific characteristics of various environmental stressors and exposure determinants. From the resulting 265 page report, targeted information about BoE, corresponding reference values (e.g., 95th percentile or measures of central tendency), exposure limit values (e.g., the German HBM I and II values) and biomonitoring equivalents (BEs) were summarized and updated. 64 individual biological, chemical, physical, psychological and social environmental stressors or exposure determinants were included to fulfil the requirements of EWAS. The list of available BoEs is extensive with a number of 135; however, 12 of the stressors and exposure determinants considered do not leave any measurable specific substance in accessible body specimens. Opportunities to estimate the internal exposure stressors not (yet) detectable in human specimens were discussed. Data about internal exposures are useful to decode the exposome. The paper provides extensive information for EWAS. Information included serves as a guideline - snapshot in time without any claim to comprehensiveness - to interpret HBM data and offers opportunities to collect information about the internal exposure of stressors if no specific BoE is available. This work has received funding from the European Union's Seventh Programme for research, technological development and demonstration under grant agreement No. 603946 (Health and Environment-wide Associations based on Large population Surveys, HEALS). All HEALS partners involved in the discussion of deliverable 4.2 during the annual HEALS meeting in Edinburgh, UK, on September 16, 2014, are grate-fully acknowledged. Special thanks go to our colleagues outside WP4 and outside HEALS who reviewed chapters of their expertise: Thank you, Tomislav Bituh, Danijela Š timac, and Matthias Weigl.

Objectives Prenatal exposure of long chain polyunsaturated fatty acids (LCPUFA) are essential for normal fetal growth and neurodevelopment. Availability of LCPUFA depends mostly on maternal fish consumption. Fish consumption also exposes the fetus to mercury which is well known neurotoxicant. We analyzed the associations of combined LCPUFA and mercury from fish consumption during pregnancy on newborn's brain measures and child neurodevelopment in a northern Adriatic coastal area. Patients and methods The prospective cohort study included 257 mother – infant pairs enrolled in a susceptible population of the Public Health Impact on long- term, low-level, Mixed Element exposure (PHIME) EU Sixth Framework Programme from 2 recruitment areas of the northern part of the Adriatic coast. Umbilical cord blood taken at delivery was used for measuring concentration of total mercury (THg) and specific LCPUFA - docosahexaenoic acid (DHA) and arachidonic acid (ARA). Neonatal cranial sonography was performed at the age of 3 days in 57 newborns. Neurodevelopmental assessment of cognitive, motor and language skills were conducted at 257 children at the age of 18 months using the Bayley Scales of Infant and Toddler Development, Third Edition. The participants were divided into two groups depending on the THg concentration in the umbilical cord blood (exposed > 5.8 μg/L and unexposed < 5.8 μg/L). Dietary habits and exposures to environmental and social factors were assessed through questionnaires. Results There is a statistically significant difference in the cerebellum length (p = 0.032) and the superior frontal gyrus width (p = 0.023) between the exposed and the unexposed group. In combined analysis, including possible protective variables as DHA and ARA (R2 = 0.22, p = 0.001), the negative contribution of THg on cerebellum length (beta = −0.16, p = 0.001) persisted. We found no correlation between THg concentration in umbilical cord blood and child neurodevelopment scores at the age of 18 months. Language score with receptive and expressive subscores was significantly associated with fish consumption (p < 0.05). Conclusion This analysis demonstrates the existence of morphological brain changes in newborns that are prenatally exposed at mercury concentrations what was diminished in combined analyse including LCPUFA. Our results emphasizes the importance of LCPUFA's and mercury common influence as a predictor of developmental outcome. Fish consumption, not solely LCPUFA contributes to better language development of children at the age of 18 months.

In recent years, several studies have addressed the issue of prenatal exposure to methylmercury (MeHg); however, few have actually analysed MeHg blood concentrations. Our study population included mothers and their new-borns from Slovenia (central region; N = 584) and Croatia (coastal region; N = 234). We have measurements of total Hg (THg) and MeHg in maternal hair, maternal peripheral blood, and cord blood. Cord blood Hg concentrations were low to moderate (median THg = 1.84 ng/g and MeHg = 1.69 ng/g). The proportion of THg as MeHg (%MeHg) in maternal and cord blood varied between 4% and 100% (coefficient of variation, CV = 32%) and between 8% and 100% (CV = 20%), respectively. Our data shows that variability of %MeHg was higher at lower blood THg levels. Concentrations of MeHg in maternal blood and cord blood were highly correlated (Rs = 0.943), in the case of inorganic Hg correlation was significant but weaker (Rs = 0.198). MeHg levels in maternal blood and cord blood were positively associated with seafood intake, maternal age, and negatively associated with pre-pregnancy BMI. Additionally, MeHg in maternal blood was positively associated with plasma selenium levels, and cord blood MeHg was negatively associated with parity. The results of multiple linear regression models showed that speciation analysis provides more defined estimation of prenatal exposure in association modelling. Associations between Hg exposure and cognitive performance of children (assessed using Bayley Scales of Infant and Toddler development) adjusted for maternal or child Apolipoprotein E genotypes showed higher model R2 and lower p-values when adjusted for MeHg compared to THg. This study demonstrates that Hg speciation improves the association between exposure and possible negative health effects. Bibliografija: str. 8-10. Abstract. ARRS ARRS, NEURODYS EU

As a consequence of over 500 years of mining and smelting activities (1490–1995), and of its natural geological occurrence, the soil in the Idrija region is highly contaminated with Hg. In order to assess the present situation regarding the Hg levels in local food samples, concentrations of total mercury (THg) and monomethyl mercury (MeHg) were determined in selected vegetables, mushrooms and fish from the Idrija Hg mine area. Hg levels in the foodstuffs analysed were not very high but were elevated compared to the levels in food from non-contaminated areas. The study showed that THg accumulates in mushrooms ( X =5680 ng/g dry weight, Min=346 ng/g dry weight, Max=17,100 dry weight) and chicory ( X =1950 ng/g dry weight, Min=86 ng/g dry weight, Max=17,100 ng/g dry weight). In addition, Se and Cd concentrations were determined by ICP-MS in those vegetable and mushroom species in which the highest Hg levels were found. The levels of Cd and Se were below the threshold levels. Based on data from previous studies, we can conclude that the levels of Hg in food have not diminished significantly during the past 15 years after closure of the Hg mine. Special attention should be given to vegetables such as chicory, representing a local seasonal vegetable eaten frequently.

The aim of the present study was to evaluate the association between prenatal exposure to mercury (Hg) and neurodevelopment of the child, taking into account genetic polymorphism of apolipoprotein E (Apoe) and other relevant confounders. Six hundred and one mother-child pairs were recruited from the central Slovenia region and 243 from Rijeka, on the Croatian coast of the northern Adriatic. The total Hg in cord blood, Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) assessment at 18 months of age and Apoe genotyping was performed on 361 children; 237 of them were from Slovenia and 124 from Croatia. The results showed negative association between low-to-moderate Hg exposure in children with normal neurodevelopmental outcome and cognitive and fine motor scores at 18 months of age as assessed by Bayley III. The Hg-related decrease in cognitive score was observed only in children carrying at least one Apoe ε4 allele, while the decrease in fine motor scores was independent of the Apoe genotype. Adjusting for selenium (Se) and lead (Pb) levels, a positive association between Se and the language score and a negative association between Pb and the motor score was observed, but not in the subgroup of children carrying the ε4 allele.

Children's blood-lead concentration (B-Pb) is well studied, but little is known about cadmium (B-Cd) and mercury (B-Hg), in particular for central Europe. Such information is necessary for risk assessment and management. Therefore, we here describe and compare B-Pb, B-Cd and B-Hg in children in six European, and three non-European cities, and identify determinants of these exposures. About 50 school children (7–14 years) from each city were recruited (totally 433) in 2007–2008. Interview and questionnaire data were obtained. A blood sample was analyzed: only two laboratories with strict quality control were used. The European cities showed only minor differences for B-Cd (geometric means 0.11–0.17 μg/L) and B-Pb (14–20 μg/L), but larger for B-Hg (0.12–0.94 μg/L). Corresponding means for the non-European countries were 0.21–0.26, 32–71, and 0.3–3.2 μg/L, respectively. For B-Cd in European samples, traffic intensity close to home was a statistically significant determinant, for B-Hg fish consumption and amalgam fillings, and for B-Pb sex (boys higher). This study shows that European city children's B-Cd and B-Pb vary only little between countries; B-Hg differs considerably, due to varying tooth restoration practices and fish intake. Traffic intensity seemed to be a determinant for B-Cd. The metal concentrations were low from a risk perspective but the chosen non-European cities showed higher concentrations than the cities in Europe. Keywords: Cadmium, Mercury, Lead, Children, Exposure, Biomonitoring

Introduction: HEALS (online access: www.heals- eu.eu) aims to refine an integrated approach to perform environment-wide association studies (EWAS) to explain the exposome for an improved understanding of the links between the genome, and disease. HEALS is at present the largest EU project on this issue. Guidelines for biomarkers of exposure (BoE) were developed to characterize internal exposures in EWAS. Methods: Fact sheets about the human biomonitoring (HBM) of selected environmental stressors were provided using >800 references in an expert-driven, distributed, narrative review process. Information regarding chemistry, effects on biological systems, exposure routes, absorption, elimination, reference values and specimens for analysis were collected. Chemical, physical, biological, social and psychological stressors were included to fulfil the requirements of EWAS. Results: Fact sheets for 56 stressors were created. While BoE are available for stressor groups like chemicals (metals, organic contaminants, mixtures, etc.), others, including electromagnetic fields, noise or UV light, do not leave any measurable substance in accessible body specimens. Some stressors cannot be measured directly but their metabolites can be analysed. The relative importance of the considered stressors was determined by a list of priorities based on science based evidence. Conclusions: In an extensive review considering various kinds of environmental stressors, strength and limitations regarding the identification of internal exposures using HBM were identified. Identifying research gaps about BoE and summarizing evidence about the importance of these stressors improves the basis for policy- making to safe human health. This work has received funding from the European Union?s Seventh Programme for research, technological development and demonstration under grant agreement No 603946 (Health and Environment-wide Associations based on Large population Surveys, HEALS).

© 2014 Elsevier Inc. All rights reserved, Within the European Environment and Health Action Plan an initiative to establish a coherent human biomonitoring approach in Europe was started. The project COPHES (COnsortium to Perform Human biomonitoring on a European Scale ) developed recommendations for a harmonized conduct of a human biomonitoring (HBM) survey which came into action as the pilot study DEMOCOPHES (DEMOnstration of a study to COordinate and Perform Human biomonitoring on a European Scale). Seventeen European countries conducted a survey with harmonized instruments for, inter alia, recruitment, fieldwork and sampling, in autumn/winter 2011/2012. Based on the countries' experiences of conducting the pilot study, following lessons learnt were compiled: the harmonized fieldwork instruments (basic questionnaire, urine and hair sampling) turned out to be very valuable for future HBM surveys on the European scale. A school approach was favoured by most of the countries to recruit school-aged children according to the established guidelines and country specific experiences. To avoid a low participation rate, intensive communication with the involved institutions and possible participants proved to be necessary. The communication material should also include information on exclusion criteria and offered incentives. Telephone contact to the participants the day before fieldwork during the survey can prevent the forgetting of appointments and first morning urine samples. To achieve comparable results on the European scale, training of interviewers in all issues of recruitment, fieldwork and sampling through information material and training sessions is crucial. A survey involving many European countries needs time for preparation and conduct. Materials for quality control prepared for all steps of recruitment, fieldwork and sampling proved to be important to warrant reliable results., The European Commission, DG for Research and Innovation (RTD) who funded COPHES in the 7th Framework programme (No. 244237) and DG Environment, who co-funded DEMOCOPHES under the LIFE+ Programme (50% – LIFE09 ENV/BE/000410) and partners from 21 countries.

© 2014 The Authors. Published by Elsevier Inc. This is an open access article under the CCBY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/)., The metal cadmium (Cd) is a widespread environmental pollutant with documented adverse effects on the kidneys and bones from long-term environmental exposure, but with insufficiently elucidated public health consequences such as risk of cardiovascular disease, hormone-related cancer in adults and developmental effects in children. This study is the first pan-European human biomonitoring project that succeeded in performing harmonized measurements of Cd in urine in a comparable way in mother–child couples from 16 European countries. The aim of the study was to evaluate the overall Cd exposure and significant determinants of Cd exposure. A study population of 1632 women (24–52 years of age), and 1689 children (5–12 years of age), from 32 rural and urban areas, was examined within a core period of 6 months in 2011–2012. Women were stratified as smokers and non-smokers. As expected, smoking mothers had higher geometric mean (gm) urinary cadmium (UCd; 0.24 µg/g crea; n=360) than non-smoking mothers (gm 0.18 µg/g crea; n=1272; p, Financially supported by the 7th EU framework programe(DGResearch – No. 244237-COPHES),LIFE+ 2009(DG Environment – LIFE09ENV/BE000410-DEMOCOPHES),with addi- tional co-funding from DEMOCOPHES partners.

© 2014 Elsevier Inc. All rights reserved., In 2011 and 2012,the COPHES/DEMOCOPHES twin projects performedt he first ever harmonized human biomonitoring survey in 17 European countries.In more than 1800 mother–child pairs,individual lifestyle data were collected and cadmium,cotinine and certain phthalate metabolites were measured in urine. Total mercury was determined in hair samples.While the main goal of the COPHES/DEMOCOPHES twin projects was to develop and test harmonized protocols and procedures,the goal of the current paper is to investigate whether the observed differences in biomarker values among the countries implementing DEMOCOPHES can be interpreted using information from external databases on environmental quality and lifestyle.In general,13 countries having implemented DEMOCOPHES provided high quality data from external sources that were relevant for interpretation purposes.However,some data were not available for reporting or were not in line with predefined specifications. Therefore,only part of the external information could be included in the statistical analyses. Nonetheless,there was a highly significant correlation between national levels of fish consumption and mercury in hair,the strength of antismoking legislation was significantly related to urinary cotinine levels,and we were able to show indications that also urinary cadmium levels were associated with environmental quality and food quality.These results again show the potential of biomonitoring data to provide added value for(the evaluation of)evidence-informed policy making., The European Commission,Belgium,DG for Research and Innovation(RTD),who is funding COPHES in the 7th Framework Programme(No.244237).DEMOCOPHES(LIFE09ENV/BE/000410)received 50% funding through the LIFE+ financial instrument of the European Union(DGENV),as well as 50% through funding received from the DEMOCOPHES partners.

For the first time in Europe, both European-wide and country-specific levels of urinary Bisphenol A (BPA) were obtained through a harmonized protocol for participant recruitment, sampling and quality controlled biomarker analysis in the frame of the twin projects COPHES and DEMOCOPHES. 674 child-mother pairs were recruited through schools or population registers from six European member states (Belgium, Denmark, Luxembourg, Slovenia, Spain and Sweden). Children (5–12 y) and mothers donated a urine sample. Information on socio-demographic characteristics, life style, dietary habits, and educational level of the parents was provided by mothers. After exclusion of urine samples with creatinine values below 300 mg/L or above 3000 mg/L, 653 children and 639 mothers remained for which BPA was measured. The geometric mean (with 95% confidence intervals) and 90th percentile were calculated for BPA separately in children and in mothers and were named “European reference values”. After adjustment for confounders (age and creatinine), average exposure values in each country were compared with the mean of the “European reference values” by means of a weighted analysis of variance. Overall geometric means of all countries (95% CI) adjusted for urinary creatinine, age and gender were 2.04 (1.87–2.24) µg/L and 1.88 (1.71–2.07) µg/L for children (n=653) and mothers (n=639), respectively. Multiple regression analysis was used to identify significant environmental, geographical, personal or life style related determinants. Consumption of canned food and social class (represented by the highest educational level of the family) were the most important predictors for the urinary levels of BPA in mothers and children. The individual BPA levels in children were significantly correlated with the levels in their mothers (r=0.265, pFor the first time in Europe, both European-wide and country-specific levels of urinary Bisphenol A (BPA) were obtained through a harmonized protocol for participant recruitment, sampling and quality controlled biomarker analysis in the frame of the twin projects COPHES and DEMOCOPHES. 674 child-mother pairs were recruited through schools or population registers from six European member states (Belgium, Denmark, Luxembourg, Slovenia, Spain and Sweden). Children (5-12y) and mothers donated a urine sample. Information on socio-demographic characteristics, life style, dietary habits, and educational level of the parents was provided by mothers. After exclusion of urine samples with creatinine values below 300mg/L or above 3000mg/L, 653 children and 639 mothers remained for which BPA was measured. The geometric mean (with 95% confidence intervals) and 90th percentile were calculated for BPA separately in children and in mothers and were named "European reference values". After adjustment for confounders (age and creatinine), average exposure values in each country were compared with the mean of the "European reference values" by means of a weighted analysis of variance. Overall geometric means of all countries (95% CI) adjusted for urinary creatinine, age and gender were 2.04 (1.87-2.24) µg/L and 1.88 (1.71-2.07) µg/L for children (n=653) and mothers (n=639), respectively. Multiple regression analysis was used to identify significant environmental, geographical, personal or life style related determinants. Consumption of canned food and social class (represented by the highest educational level of the family) were the most important predictors for the urinary levels of BPA in mothers and children. The individual BPA levels in children were significantly correlated with the levels in their mothers (r=0.265, p

Susceptibility to environmental stressors has been described for fetal and early childhood development. However, the possible susceptibility of the prepubertal period, characterized by the orchestration of the organism towards sexual maturation and adulthood has been poorly investigated and exposure data are scarce. In the current study levels of cadmium (Cd), cotinine and creatinine in urine were analyzed in a subsample 216 children from 12 European countries within the DEMOCOPHES project. The children were divided into six age-sex groups: boys (6-8 years, 9-10 years and 11 years old), and girls (6-7 years, 8-9 years, 10-11 years). The number of subjects per group was between 23 and 53. The cut off values were set at 0.1µg/L for Cd, and 0.8µg/L for cotinine defined according to the highest limit of quantification. The levels of Cd and cotinine were adjusted for creatinine level. In the total subsample group, the median level of Cd was 0.180µg/L (range 0.10-0.69µg/L), and for cotinine the median wet weight value was 1.50µg/L (range 0.80-39.91µg/L). There was no significant difference in creatinine and cotinine levels between genders and age groups. There was a significant correlation between levels of cadmium and creatinine in all children of both genders. This shows that even at such low levels the possible effect of cadmium on kidney function was present and measurable. An increase in Cd levels was evident with age. Cadmium levels were significantly different between 6-7 year old girls, 11 year old boys and 10-11 year old girls. As there was a balanced distribution in the number of subjects from countries included in the study, bias due to data clustering was not probable. The impact of low Cd levels on kidney function and gender differences in Cd levels needs further investigation. publisher: Elsevier articletitle: Gender differences in cadmium and cotinine levels in prepubertal children journaltitle: Environmental Research articlelink: http://dx.doi.org/10.1016/j.envres.2014.10.008 content_type: article copyright: Copyright © 2014 Elsevier Inc. All rights reserved. ispartof: Environmental Research vol:141 pages:125-31 ispartof: location:Netherlands status: published

© 2014 Elsevier Inc. All rights reserved., In 2004 the European Commission and Member States initiated activities towards a harmonized approach for Human Biomonitoring surveys throughout Europe. The main bjective was to sustain environmental health policy by building a coherent and sustainable framework and by increasing the comparability of data across countries. A pilot study to test common guidelines for setting up surveys was considered a key step in this process. Through a bottom-up approach that included all stakeholders, a joint study protocol was elaborated. From September 2011 till February 2012, 17 European countries collected data from 1844 mother–child pairs in the frame of DEMOnstration of a study to COordinate and Perform Human Biomonitoring on a European Scale (DEMOCOPHES).1 Mercury in hair and urinary cadmium and cotinine were selected as biomarkers of exposure covered by sufficient analytical experience. Phthalate metabolites and Bisphenol A in urine were added to take into account increasing public and political awareness for emerging types of contaminants and to test less advanced markers/markers covered by less analytical experience. Extensive efforts towards chemo-analytical comparability were included. The pilot study showed that common approaches can be found in a context of considerable differences with respect to experience and expertize, socio-cultural background, economic situation and national priorities. It also evidenced that comparable Human Biomonitoring results can be obtained in such context. A European network was built, exchanging information, expertize and experiences, and providing training on all aspects of a survey. A key challenge was finding the right balance between a rigid structure allowing maximal comparability and a flexible approach increasing feasibility and capacity building. Next steps in European harmonization in Human Biomonitoring surveys include the establishment of a joint process for prioritization of substances to cover and biomarkers to develop, linking biomonitoring surveys with health examination surveys and with research, and coping with the diverse implementations of EU regulations and international guidelines with respect to ethics and privacy., Financial support: COPHES (COnsortium to Perform Human Biomonitoring on a European Scale) was funded by the Seventh EU Framework Programme 2007–2011 under grant agreement no [244237]. DEMOCOPHES (DEMOnstration of a study to COordinate and Perform Human Biomonitoring on a European Scale) was co-funded (50%:50%) by the European Commission LIFE+ Programme (LIFE09/ENV/BE/000410) and the partners.

© 2014 Published by Elsevier Inc., A communication strategy was developed by The Consortium to Perform Human Biomonitoring on a European Scale (COPHES), as part of its objectives to develop a framework and protocols to enable the collection of comparable human biomonitoring data throughout Europe. The framework and protocols were tested in the pilot study DEMOCOPHES (Demonstration of a study to Coordinate and Perform Human biomonitoring on a European Scale). The aims of the communication strategy were to raise awareness of human biomonitoring, encourage participation in the study and to communicate the study results and their public health significance. It identified the audiences and key messages, documented the procedure for dissemination of results and was updated as the project progressed. A communication plan listed the tools and materials such as press releases, flyers, recruitment letters and information leaflets required for each audience with a time frame for releasing them. Public insight research was used to evaluate the recruitment material, and the feedback was used to improve the documents. Dissemination of results was coordinated in a step by step approach by the participating countries within DEMOCOPHES, taking into account specific national messages according to the needs of each country. Participants received individual results, unless they refused to be informed, along with guidance on what the results meant. The aggregate results and policy recommendations were then communicated to the general public and stakeholders, followed by dissemination at European level. Several lessons were learnt that may assist other future human biomonitoring studies. Recruitment took longer than anticipated and so social scientists, to help with community engagement, should be part of the research team from the start. As a European study, involving multiple countries, additional considerations were needed for the numerous organisations, different languages, cultures, policies and priorities. Therefore, communication documents should be seen as templates with essential information clearly indicated and the option for each country to tailor the material to reflect these differences. Future studies should consider setting up multidisciplinary networks of medical professionals and communication experts, and holding training workshops to discuss the interpretation of results and risk communication. Publicity and wide dissemination of the results helped to raise awareness of human biomonitoring to the general public, policy makers and other key stakeholders. Effective and timely communication, at all stages of a study, is essential if the potential of human biomonitoring research to improve public health is to be realised., COPHES was coordinated by BiPRO GmbH, Germany, with the University of Leuven, Belgium and was funded by DG Research in the Seventh Framework Programme (FP7/2007-2013). DEMOCOPHES (LIFE09 ENV/BE/000410) was coordinated by the Federal Public Service, Health, Food Chain Safety and Environment, Belgium and was jointly financed by the European Commission LIFE ┼ programme (50%) and partners from 21 countries. Information on the national co-funding institutions is accessible via the ‘Partners’ page of the DEMOCOPHES website. Each country obtained appropriate ethical approval for the DEMOCOPHES study. In the UK, the research was approved by the London Riverside South West Research Ethics Committee (reference 11/LO/1383) prior to commencement of the study.

© 2014 Elsevier Inc. All rights reserved., The potential of Human Biomonitoring (HBM) in exposure characterisation and risk assessment is well established in the scientific HBM community and regulatory arena by many publications. The European Environment and Health Strategy as well as the Environment and Health Action Plan 2004-2010 of the European Commission recognised the value of HBM and the relevance and importance of coordination of HBM programmes in Europe. Based on existing and planned HBM projects and programmes of work and capabilities in Europe the Seventh Framework Programme (FP 7) funded COPHES (COnsortium to Perform Human Biomonitoring on a European Scale) to advance and improve comparability of HBM data across Europe. The pilot study protocol was tested in 17 European countries in the DEMOCOPHES feasibility study (DEMOnstration of a study to COordinate and Perform Human biomonitoring on a European Scale) cofunded (50%) under the LIFE+ programme of the European Commission. The potential of HBM in supporting and evaluating policy making (including e.g. REACH) and in awareness raising on environmental health, should significantly advance the process towards a fully operational, continuous, sustainable and scientifically based EU HBM programme. From a number of stakeholder activities during the past 10 years and the national engagement, a framework for sustainable HBM structure in Europe is recommended involving national institutions within environment, health and food as well as European institutions such as ECHA, EEA, and EFSA. An economic frame with shared cost implications for national and European institutions is suggested benefitting from the capacity building set up by COPHES/DEMOCOPHES., COPHES was coordinated by BiPRO GmbH, Germany, with the University of Leuven, Belgium and was funded by DG Research in the Seventh Framework Programme (FP7/2007-2013). DEMOCOPHES (LIFE09 ENV/BE/000410) was coordinated by the Federal Public Service Health, Food Chain Safety and Environment, Belgium and was jointly financed by the European Commission LIFE┼ programme (50%) and national institutions in each participating country.

In order to assess mercury (Hg), selenium (Se) and arsenic (As) exposure in the Mediterranean area, total mercury (THg), monomethylmercury (MeHg), Se and As levels were measured in umbilical cord blood and breast milk from Italian (n=900), Slovenian (n=584), Croatian (n=234) and Greek (n=484) women. THg, MeHg, As, and Se levels were also determined in blood samples of the same mothers from Italy and Croatia. In addition, THg and MeHg were determined in the same women's hair from all the countries involved in this study and As and Se levels were determined in the mother's urine samples from Italy, Croatia and Greece. Besides recording the consumption of other food items, the frequencies of fish consumption were assessed by detailed food frequency questionnaires, since fish represents an important source of Hg, Se and As in humans. The highest levels of THg and As were found in cord blood (Med((THg))=5.8 ng/g; Med((As))=3.3 ng/g) and breast milk (Med((THg))=0.6 ng/g; Med((As))=0.8 ng/g) from Greek women, while the highest Se levels were found in cord blood (Med=113 ng/g) from Italy. Significant linear correlations were found between Hg, Se and As in blood, cord blood and breast milk. In addition, significant relations were found between the frequencies of total fish consumption and biomarkers of As, MeHg and Se exposure, with the strongest Spearman rank coefficients between frequencies of total fish consumption and THg levels in cord blood (r(s)=0.442, p

Different forms of dripstones formed on concrete surfaces were collected in different environmental (open-space vs. karstic cave) and climatic (Mediterranean vs. continental) conditions. Spherulitic and rhombohedronic microstructures in dripstones result from changes in the saturation state of the mother solution from which they are formed. Alternations of dark and light laminas indicate growth in dry and wet periods. Large range of δ13C and δ18O values of dripstones was found in different environments (roughly -35.0 to -5.8 ‰ and -22.5 to -5.0 ‰ VPDB, respectively). A strong positive correlation between δ13C and δ18O values indicates isotopic disequilibrium precipitation of CaCO3. The main source of carbon is atmospheric CO2, however, large isotopic differences in δ13C values could also be ascribed to changes in solution pH and different precipitation rates. Increased δ carbon and oxygen values from the apex down the flanks presumably result from the decreasing saturation state of the solution and precipitation rate.

Background and Aims: The effects of prenatal, low-level mercury exposure through fish consumption on neurodevelopment have been studied in several populations leading to inconsistent findings. To e...

In order to assess the mercury exposure of pregnant and lactating women in Slovenia, levels of total mercury (THg) and methylmercury (MeHg) were determined in hair, cord blood and breast milk. In addition, the frequency of fish consumption was estimated, because fish is generally the main pathway for human exposure to MeHg. Hair samples were collected from 574 women participating in this study, while cord blood and breast milk samples were collected from 446 and 284 women, respectively. As expected, the levels of THg in hair (median (Med)=297 ng/g, 10th percentile (P10)=73 ng/g, 90th percentile (P90)=781 ng/g), cord blood (Med=1.5 ng/g, P10=0.5 ng/g, P90=4.2 ng/g) and breast milk (Med=0.2 ng/g, P10=0.06 ng/g, P90=0.6 ng/g) were low, due to low consumption of fish ( X =25 g/day). A significant linear correlation was found between levels of ln THg in hair and ln THg in cord blood ( r =0.87, 95% confidence interval (CI): 0.84–0.89), between levels of ln THg in hair and ln MeHg in cord blood ( r =0.94, 95% CI: 0.90–0.96) and between ln THg levels in cord blood and ln THg levels in breast milk ( r =0.36, 95% CI: 0.25–0.47). Spearman's rank correlations between the frequency of fish consumption and THg in hair ( r s =0.35, 95% CI: 0.28–0.42), and between the frequency of fish consumption and THg in cord blood ( r s =0.43, 95% CI: 0.36–0.51) or MeHg in cord blood ( r s =0.31, 95% CI: 0.06–0.52) were weak. This could be due to the approximate information on fish consumption obtained from the questionnaires, the high variability of MeHg concentrations in fish and a relatively high proportion of inorganic mercury in the biomarkers which originates from sources other than fish. In conclusion, THg levels in cord blood, THg levels in hair and MeHg levels in cord blood are suitable biomarkers of low-level Hg exposure through fish consumption. Compared to cord blood, hair samples are easy to collect, store and analyse.

The present study reports one of the few cases in which organophosphate (OP) and pyrethroid (PYR) pesticide human exposure is evaluated in family contexts by the analysis of mother/child pair samples. Urinary concentrations of 6 organic metabolites of organophosphates and 2 pyrethroids were measured in mothers and their 7-to 8-year-old children (n = 168) in a general population from the central area of Slovenia. The results were adjusted for specific gravity and creatinine. The most abundant OP metabolite in children was 4-nitrophenol (PNP) (median 0.7 ng/ml) and in mothers (0.45 ng/ml), representing parathion exposure. 3-Phenoxibenzoic acid (3-PBA) (0.26 ng/ml), the general metabolite of pyrethroids, and 3,5,6-trichloro-2-pyridinol (TCPY) (0.16 ng/ml; chlorpyriphos) were the second most abundant compounds in children and mothers, respectively. The geometric mean specific gravity adjusted concentrations of OPs and PYRs were statistically significantly higher in children than in their mothers (between 3% and 24% higher), with the exception of TCPY (26% lower). All OP and PYR metabolites found in higher concentration in children showed significant positive correlations with the metabolite concentrations found in the mothers (p < 0.05 and 0.01), involving the fact that higher maternal concentrations were associated with higher children levels. These differential mother-children distributions and significant correlations were observed for the 2 types of pesticides studied, OPs and PYRs, which have different chemical properties. This agreement is consistent with the incorporation of the pesticides because of the general activities developed in the family context, instead of pesticide-dependent specific inputs. Comparison of the estimated daily intakes with the acceptable daily intakes of all detected metabolites revealed no significant risk of adverse health effects from exposure to these pesticides. © 2019 The Authors, The authors are grateful to all women who participated in the study, the participating hospital for the data sampling and all the field workers for their enthusiastic efforts. This paper was supported by the European Union project CROME (LIFE12 ENV/GR/001040 ). Additional funding was received from the European Union projects: HEALS ( FP7-ENV-2013-603946 ), PHIME ( FOOD-CT-2006-016253 ), Neurosome ( H2020-MSCA-ITN-2017 SEP-210411486 ) and EDC-MET ( H2020-HEALTH/0490-825762 ) and the Slovenian Research Agency–ARRS (program P1-0143 ; project NEURODYS–contract no. JZ-9400 ). Appendix A