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Background: Exposure to air pollution during pregnancy has been associated with adverse pregnancy outcomes in studies worldwide, other studies have described beneficial effects of residential greenspace on pregnancy outcomes. The biological mechanisms that underlie these associations are incompletely understood. Recent studies have shown that a biological stress response, with release of cortisol, may underlie associations between air pollution and health effects. The available research on air pollution exposure in relation to biological stress during pregnancy is still scarce. Methods: We explored associations between residential exposure to air pollution, access to neighborhood greenspace and hair cortisol concentrations in a prospective pregnancy cohort study. We modelled participants’ residential air pollutant concentrations (particulate matter with an aerodynamic diameter ≤ 2.5 μm, nitrogen dioxide (NO2), black carbon (BC)), assessed residential distance to a major road and access to a neighborhood greenspace. Hair cortisol concentrations, reflecting cortisol secretion over a period of 3 months prior to sampling, were determined at the end of the second (n = 133) and third pregnancy trimester (n = 81). Results: Three-month mean residential NO2 and BC concentrations were positively associated with third pregnancy trimester hair cortisol concentrations. The residential distance to a major road was negatively associated with second and third trimester hair cortisol concentrations. Access to a greenspace of 10 hectares or more within 800 meters travel distance significantly moderated the association between residential proximity to a major road and second trimester hair cortisol concentrations. At an average residential distance of 304 meters from a major road, mean second trimester HCC were estimated 22% lower for mothers with access to a neighborhood greenspace (3.71 (95% CI: 3.24, 4.24) pg/mg hair) compared to mothers without access (4.22 (95% CI: 3.26, 5.47) pg/mg hair). The moderation tended towards significance in the third trimester (p < 0.10). Conclusions: Increased residential exposure to air pollution and closer proximity to a major road are associated with an increased biological stress response in the second and third trimester of pregnancy, access to neighborhood greenspace may moderate the association. Trial registration: The IPANEMA study is registered under number NCT02592005 at clinicaltrials.gov.

Background: It has been suggested that prenatal exposure to n-3 long-chain fatty acids protects against asthma and other allergy-related diseases later in childhood. The extent to which fish intake in pregnancy protects against child asthma and rhinitis symptoms remains unclear. We aimed to assess whether fish and seafood consumption in pregnancy is associated with childhood wheeze, asthma and allergic rhinitis. Methods: We pooled individual data from 60 774 mother-child pairs participating in 18 European and US birth cohort studies. Information on wheeze, asthma and allergic rhinitis prevalence was collected using validated questionnaires. The time periods of interest were: infancy (0-2 years), preschool age (3-4 years), and school age (5-8 years). We used multivariable generalized models to assess associations of fish and seafood (other than fish) consumption during pregnancy with child respiratory outcomes in cohort-specific analyses, with subsequent random-effects meta-analyses. Results: The median fish consumption during pregnancy ranged from 0.44 times/week in The Netherlands to 4.46 times/week in Spain. Maternal fish intake during pregnancy was not associated with offspring wheeze symptoms in any age group nor with the risk of child asthma [adjusted meta-analysis relative risk (RR) per 1-time/week = 1.01, 95% confidence interval 0.97-1.05)] and allergic rhinitis at school age (RR = 1.01, 0.99-1.03). These results were consistently found in further analyses by type of fish and seafood consumption and in sensitivity analyses. Conclusion: We found no evidence supporting a protective association of fish and seafood consumption during pregnancy with offspring symptoms of wheeze, asthma and allergic rhinitis from infancy to mid childhood. This work was supported by the European Community’s Seventh Framework Program [EU- FP7- HEALTH-2009-single-stage-241604]. Details of funding per cohort are available at IJE online.

In epidemiological studies on the toxic effects of prenatal exposure to hexachlorobenzene (HCB), researchers report HCB concentrations, either as wet-weight or per lipid weight basis, in matrices like breast milk, and maternal and cord blood. Conversion of exposures across matrices is needed for comparisons of concentrations and dose effect across cohorts. Using data from a birth cohort study in eastern Slovakia, we derived the maternal blood to cord blood HCB concentration ratio utilizing measured concentrations in 1027 paired maternal and cord blood samples, on a per-lipid basis. In addition to data from the Slovak study, the maternal milk to maternal serum ratio was summarized from 23 published studies on partitioning of HCB between human milk lipid and blood lipid. We identified two distinct groups of milk:blood ratios, those ≤0.45 and those ≥0.85. We assumed that using partition ratios ≤0.45 will underestimate HCB exposure estimates. Taking into account this precautionary measure, we suggest a conversion ratio of 1.21, which is the median of the 16 ratios identified in our literature review. We consider our estimate as conservative and providing appropriate safety in risk analysis.

Background: Placental mitochondrial DNA (mtDNA) content can be indicative of oxidative damage to the placenta during fetal development and is responsive to external stressors. In utero exposure to environmental pollutants that may influence placental mtDNA needs further exploration. Objectives: We evaluated if placental mtDNA content is altered by environmental pollution in newborns and identified pollutants independently associated to alterations in placental mtDNA content. Methods: mtDNA content was measured in placental tissue of 233 newborns. Four perfluoroalkyl compounds and nine organochlorine compounds were quantified in cord blood plasma samples and six toxic metals in whole cord blood. We first applied a LASSO (least absolute shrinkage and selection operator) penalized regression model to identify independent associations between environmental pollutants and placental mtDNA content, without penalization of several covariates. Then adjusted estimates were obtained using an ordinary least squares (OLS) regression model evaluating the pollutants' association with placental mtDNA content, adjusted for several covariates. Results: Based on LASSO penalized regression, oxychlordane, p,p′-dichlorodiphenyldichloroethylene, β-hexachlorocyclohexane, perfluorononanoic acid, arsenic, cadmium and thallium were identified to be independently associated with placental mtDNA content. The OLS model showed a higher placental mtDNA content of 2.71% (95% CI: 0.3 to 5.2%; p=0.03) and 1.41% (0.1 to 2.8%, p=0.04) for a 25% concentration increase of respectively cord blood β-hexachlorocyclohexane and arsenic. For a 25% concentration increase of cord blood thallium, a 4.88% lower placental mtDNA content (95% CI: -9.1 to −0.5%, p=0.03) was observed. Conclusion: In a multi-pollutant approach, low fetal exposure levels of environmental organic and inorganic pollutants might compromise placental mitochondrial function as exemplified in this study by alterations in mtDNA content. Keywords: Placenta, Mitochondrial DNA content, Environmental pollution, Newborns

Background: The Flemish Environment and Health Studies (FLEHS) are human biomonitoring surveys running in Flanders since 1999. Additionally to biomarkers of exposure, markers of genotoxicity and oxidative stress have been measured, including the alkaline comet and micronucleus assay in peripheral whole blood cells, and urinary concentrations of 8-oxo-2′-deoxyguanosine (8-oxodG). Aim: Exposure-effect associations were explored in a pooled dataset of nine different cross-sectional FLEHS surveys. Data of adolescents collected in a time frame of about 20 years (1999–2018) were compiled. The aim of the study was to examine whether increased variation in exposure, lifestyle and environmental factors would lead to more powerful and robust exposure-effect associations. Materials & methods: The biomarkers were measured in 2283 adolescents in the age range of 14–18 years. Exposure to polycyclic aromatic hydrocarbons [1-hydroxypyrene (1-OHP)], benzene (tt’-muconic acid), metals (arsenic, cadmium, copper, nickel, thallium, lead, chromium), persistent organochlorines and phthalates were assessed in blood or urine. Furthermore, outdoor air levels of particulate matter (PM10 and PM2.5) at the residences of the youngsters were calculated. Pooled statistical analysis was done using mixed models. Study-specific differences in the genotoxicity markers and in the strength/direction of the association were accounted for. This was done by incorporating the random factor ‘study’ and a random study slope (if possible). The exposure markers were centered around the study-specific mean in order to correct for protocol changes over time. Results: A significant association was observed for the urinary oxidative stress marker 8-oxodG, which was positively associated with 1-OHP (5% increase for doubling of 1-OHP levels, p = 0.001), and with urinary copper (26% increase for doubling of copper levels, p = 0.001), a metal involved in the Fenton reaction in biological systems. 8-oxodG was also associated with the sum of the metabolites of the phthalate di(2-ethylhexyl) phthalate (DEHP) (3% increase for doubling of the DEHP levels, p = 0.02). For those associations, data pooling increased the statistical power. However, some of the associations in the individual surveys, were not confirmed in the pooled analysis (such as comet assay and 8-oxodG vs. atmospheric PM; and 8-oxodG vs. urinary nickel). This may be due to inconsistencies in exposure-effect relations and/or variations in the pollutant mix over time and regions. Conclusion: Pooled analysis including a large population of 2283 Flemish adolescents showed that 8-oxodG, a marker of oxidative DNA damage is a valuable marker to assess impact of daily life pollutants, such as PAHs, Cu and the phthalate DEHP.

Because of their dirt-, water- and oil-repelling properties, per- and polyfluoroalkyl substances (PFASs) are frequently used in a broad variety of consumer products. They have been detected in human samples worldwide. In Flanders, Belgium, the Flemish Environment and Health Studies (FLEHS) measured the levels of five PFAS biomarkers in four different age groups of the Flemish population and identified determinants of variability in exposure. Cord plasma or peripheric serum samples and questionnaire data were available for 220 mother-newborn pairs (2008-2009), 269 mother-newborn pairs (2013-2014), 199 adolescents (14-15 years old, 2010), 201 adults (20-40 years old, 2008-2009) and 205 adults (50-65 years old, 2014). Measured levels of perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) in Flanders are in the middle or low range compared to concentrations reported in other Western countries. Levels of perfluorobutanesulfonic acid (PFBS) were below the quantification limit in 98%-100% of the samples. Despite decreasing levels in time for PFOS and PFOA, 77% of the adults (2014) had serum levels exceeding HBM-I values of 5 mu/L for PFOS and 2 mu g/L for PFOA. Beside age, sex, fish consumption, parity and breastfeeding, the multiple regression models identified additionally consumption of offal and locally grown food, and use of cosmetics as possible exposures and menstruation as a possible route of elimination. Better knowledge on determinants of exposure is essential to lower PFASs exposure. This paper is based on research conducted within the framework of the Flemish Centre of Expertise on Environment and Health, funded by the Environment, Nature and Energy Department of the Flemish government, the Department of Public Health and the Department of Science of the Flemish government. The views expressed herein are those of the authors and are not necessarily endorsed by the Flemish government. Colles, A (reprint author), VITO Hlth, Boeretang 200, B-2400 Mol, Belgium. ann.colles@vito.be

Background: Phthalates, bisphenol A (BPA) and triclosan (TCS) are detectable in the vast majority of people. Most humans are continuously exposed to these chemicals due to their presence in food or in everyday consumer products. The measurement of these compounds in family members may help to explore the impact of major lifestyle factors on exposure. Mothers and (young) children are especially interesting to study, as they mostly share considerable parts of daily life together. Materials and methods: Phthalate metabolites, bisphenol A (BPA) and triclosan (TCS) were measured in first morning void urine, collected in mother-child pairs (n = 129) on the same day. The mothers (27-45y) and their children (6-11y) were recruited in the Brussels agglomeration and rural areas of Belgium in the context of the European COPHES-DEMOCOPHES human biomonitoring project. Face-to-face questionnaires gathered information on major exposure sources and lifestyle factors. Exposure determinants were assessed by multiple linear regression analysis. Results: The investigated compounds were detectable in nearly all mothers (92.8–100%) and all children (95.2–100%). The range (P90 vs. P10) of differences in urinary concentrations within each age group was for most compounds around 10–20 fold, and was very high for TCS up to 35 and 350-fold in children and mothers respectively. Some participants exceeded the tolerable daily intake guidelines as far as they were available from the European Food Safety Authority (EFSA). Overall, for BPA, the urinary concentrations were similar among both age groups. Most urinary phthalate metabolites were higher in children compared to the mothers, except for monoethyl phthalate (MEP). TCS levels were generally higher in the mothers. Despite the difference in mothers' and children's urinary concentrations, the creatinine-corrected levels were correlated for all biomarkers (Spearman rank r = 0.32 to 0.66, p < 0.001). Furthermore, for phthalates, similar home and lifestyle factors were associated with the urinary concentrations in both age groups: home renovation during last two years or redecoration during the last year for di-ethyl phthalate (DEP); PVC in home for di-n-butyl phthalate (DnBP), di-iso-butyl phthalate (DiBP) and butyl benzyl phthalate (BBzP), and personal care products use for DiBP and DnBP. Based on questionnaire information on general food type consumption patterns, the exposure variability could not be explained. However, comparing the phthalate intake from the current study with earlier assessed Belgian food intake calculations for both ages, food in general was estimated to be the major intake source for di-ethyl hexyl phthalate (DEHP), with diminishing importance for BBzP, DiBP and DnBP. Conclusion: Our results confirm, that children and their mothers, sharing diets and home environments, also share exposure in common consumer products related chemicals. By collecting morning urine levels on the same day, and using basic questionnaires, suspected exposure routes could be unraveled.

To follow time trends in exposure to environmental chemicals, three successive campaigns of the Flemish Environment and Health Study (FLEHS) have recruited and sampled in total 5825 participants between 2002 and 2014. Cord samples from newborns, urine and blood samples from 14 to 15 years old adolescents and from adults between 50 and 65 years old were analysed in geographical representative samples of the Flemish population. The data of the different campaigns were considered per age group and per biomarker after adjustment for predefined covariates to take into account differences in characteristics of the study populations over time. Geometric means were calculated. Multiple linear regression was used to evaluate time trends. The concentration of serum biomarkers for persistent organic pollutants (POPs), such as marker polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (p,p'-DDE), the major metabolite of dichlorodiphenyltrichloroethane (DDT), and hexachlorobenzene (HCB) expressed per g lipid, decreased significantly with time. The levels of DDE in all age groups and those of PCBs in cord and adolescent serum samples were almost halved in a time period of ten years. HCB levels were reduced by a factor of 4 in adolescents and in adults. Mean serum concentrations of the more recently regulated perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were significantly lower in cord samples of 2013 compared to samples of 2007. The decline was more pronounced for PFOS than for PFOA. In the same period, mean metabolite levels of di-2-ethylhexyl phthalate (DEHP) and of di-n-butyl phthalate (DBP) decreased significantly in urine samples of adolescents with sharper declines for DEHP than for DBP. Cadmium and lead levels in cord and adolescent blood samples were significantly lower in the recent campaigns than 10 years before. Also the mean urinary cadmium level in adults was 35% lower compared to adult samples of 2002. Such favourable trends were not observed for arsenic and thallium measured in cord blood. Similar, the concentrations of 1-hydroxypyrene, a marker for exposure to poly cyclic aromatic hydrocarbons (PAHs), was not lower in urine from adolescents sampled in 2013 compared to 2003. In contrast, concentrations of t,t'-muconic acid, a marker of benzene exposure, showed clearly reduced levels. The FLEHS program shows that concentrations of well-regulated chemicals especially traditional POPs and cadmium and lead are decreasing in the population of Flanders. Response to regulatory measures seems to happen rapid, since concentrations in humans of specific regulated perfluorinated compounds and phthalates were significantly reduced in five years time. Biomarker concentrations for arsenic, thallium, and polyaromatic hydrocarbons are not decreasing in this time span and further follow up is warranted. (C) 2016 Published by Elsevier GmbH.

Background We investigated whether human environmental exposure to chemicals that are labeled as (potential) carcinogens leads to increased (oxidative) damage to DNA in adolescents. Material and methods Six hundred 14–15-year-old youngsters were recruited all over Flanders (Belgium) and in two areas with important industrial activities. DNA damage was assessed by alkaline and formamidopyrimidine DNA glycosylase (Fpg) modified comet assays in peripheral blood cells and analysis of urinary 8-hydroxydeoxyguanosine (8-OHdG) levels. Personal exposure to potentially carcinogenic compounds was measured in urine, namely: chromium, cadmium, nickel, 1-hydroxypyrene as a proxy for exposure to other carcinogenic polycyclic aromatic hydrocarbons (PAHs), t,t-muconic acid as a metabolite of benzene, 2,5-dichlorophenol (2,5-DCP), organophosphate pesticide metabolites, and di(2-ethylhexyl) phthalate (DEHP) metabolites. In blood, arsenic, polychlorinated biphenyl (PCB) congeners 118 and 156, hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (DDT) and perfluorooctanoic acid (PFOA) were analyzed. Levels of methylmercury (MeHg) were measured in hair. Multiple linear regression models were used to establish exposure-response relationships. Results Biomarkers of exposure to PAHs and urinary chromium were associated with higher levels of both 8-OHdG in urine and DNA damage detected by the alkaline comet assay. Concentrations of 8-OHdG in urine increased in relation with increasing concentrations of urinary t,t-muconic acid, cadmium, nickel, 2,5-DCP, and DEHP metabolites. Increased concentrations of PFOA in blood were associated with higher levels of DNA damage measured by the alkaline comet assay, whereas DDT was associated in the same direction with the Fpg-modified comet assay. Inverse associations were observed between blood arsenic, hair MeHg, PCB 156 and HCB, and urinary 8-OHdG. The latter exposure biomarkers were also associated with higher fish intake. Urinary nickel and t,t-muconic acid were inversely associated with the alkaline comet assay. Conclusion This cross-sectional study found associations between current environmental exposure to (potential) human carcinogens in 14–15-year-old Flemish adolescents and short-term (oxidative) damage to DNA. Prospective follow-up will be required to investigate whether long-term effects may occur due to complex environmental exposures.

The broadly used industrial chemical bisphenol A (BPA), applied in numerous consumer products, has been under scrutiny in the past 20 years due to its widespread detection in humans and the environment and potential detrimental effects on human health. Following implemented restrictions and phase-out initiatives, BPA is replaced by alternative bisphenols, which have not received the same amount of research attention. As a part of the fourth cycle of the Flemish Environment and Health Study (FLEHS IV, 2016–2020), we monitored the internal exposure to six bisphenols in urine samples of 423 adolescents (14–15 years old) from Flanders, Belgium. All measured bisphenols were detected in the study population, with BPA and its alternatives bisphenol F (BPF) and bisphenol S (BPS) showing detection frequencies > 50%. The reference values show that exposure to these compounds is extensive. However, the urinary BPA level decreased significantly in Flemish adolescents compared to a previous cycle of the FLEHS (2008–2009). This suggests that the replacement of BPA with its analogues is ongoing. Concentrations of bisphenols measured in the Flemish adolescents were generally in the same order of magnitude compared to recent studies worldwide. Multiple regression models were used to identify determinants of exposure based on information on demographic and lifestyle characteristics of participants, acquired through questionnaires. Some significant determinants could be identified: sex, season, smoking behavior, educational level of the parents, recent consumption of certain foods and use of certain products were found to be significantly associated with levels of bisphenols. Preliminary risk assessment showed that none of the estimated daily intakes (EDIs) of BPA exceeded the tolerable daily intake, even in a high exposure scenario. For alternative bisphenols, no health-based guidance values are available, but in line with the measured urinary levels, their EDIs were lower than that of BPA. This study is, to the best of our knowledge, the first to determine internal exposure levels of other bisphenols than BPA in a European adolescent population.

The European Joint Programme HBM4EU is the backbone for knowledge on human exposure to environmental chemicals in the EU. It will inform European and national policy makers to take science based de...

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

Background Infant exposure to persistent organic pollutants (POPs) may contribute to obesity. However, many studies so far have been small, focused on transplacental exposure, used an inappropriate measure to assess postnatal exposure through breastfeeding if any, or did not discern between prenatal and postnatal effects. Objectives We investigated prenatal and postnatal exposure to POPs and infant growth (a predictor of obesity). Methods We pooled data from seven European birth cohorts with biomarker concentrations of polychlorinated biphenyl 153 (PCB-153) (n = 2,487), and p,p´-dichlorodiphenyldichloroethylene (p,p´-DDE) (n = 1,864), estimating prenatal and postnatal POPs exposure using a validated pharmacokinetic model. Growth was change in weight-for-age z-score between birth and 24 months. Per compound, multilevel models were fitted with either POPs total exposure from conception to 24 months or prenatal or postnatal exposure. Results We found a significant increase in growth associated with p,p´-DDE, seemingly due to prenatal exposure (per interquartile increase in exposure, adjusted β = 0.12; 95% CI: 0.03, 0.22). Due to heterogeneity across cohorts, this estimate cannot be considered precise, but does indicate that an association with infant growth is present on average. In contrast, a significant decrease in growth was associated with postnatal PCB-153 exposure (β = –0.10; 95% CI: –0.19, –0.01). Conclusion To our knowledge, this is the largest study to date of POPs exposure and infant growth, and it contains state-of-the-art exposure modeling. Prenatal p,p´-DDE was associated with increased infant growth, and postnatal PCB-153 with decreased growth at European exposure levels. Citation Iszatt N, Stigum H, Verner MA, White RA, Govarts E, Palkovicova Murinova L, Schoeters G, Trnovec T, Legler J, Pelé F, Botton J, Chevrier C, Wittsiepe J, Ranft U, Vandentorren S, Kasper-Sonnenberg M, Klümper C, Weisglas-Kuperus N, Polder A, Eggesbø M, OBELIX. 2015. Prenatal and postnatal exposure to persistent organic pollutants and infant growth: a pooled analysis of seven European birth cohorts. Environ Health Perspect 123:730–736; http://dx.doi.org/10.1289/ehp.1308005

BACKGROUND: Various studies report interactions between thyroid hormones and early life chemical exposure. Our objective was to analyse associations between markers of endocrine disrupting chemical exposure and thyroid function in newborns, determined in heel prick blood spots.METHODS: Three European mother-child cohorts (FLEHSI - Belgium, HUMIS - Norway, and the PCB cohort - Slovakia. Total n=1784) were pooled for the purpose of this study. Data on Thyroid Stimulating Hormone (TSH) was obtained from national neonatal screening registries, and cord plasma and/or breast milk was collected to determine exposure to various chemicals. Multiple regression models were composed with exposure and cohort as fixed factors, and adjustments were made for a priori defined covariates.RESULTS: Median TSH concentrations were 1.00, 1.10, and 2.76 mU/l, for the Belgian, Norwegian, and the Slovak cohort, respectively. For polychlorinated biphenyl (PCB)-153 and dichlorodiphenyldichloroethylene (p,p'-DDE), children in the third exposure quartiles had a 12 - 15% lower TSH at birth. Results remained unchanged after additional adjustment for birth weight and gestational weight gain. No effect on TSH was observed for the other compounds.CONCLUSION: Early life exposure to PCB-153, and p,p'-DDE was associated with newborn TSH levels. Higher exposure levels were associated with 12-15% lower TSH levels.Pediatric Research (2017); doi:10.1038/pr.2017.50.

The study aim was to investigate the association between prenatal exposure to endocrine disrupting chemicals (EDCs) and the body composition of 7 to 9 year old Flemish children. The subjects were 114 Flemish children (50% boys) that took part in the first Flemish Environment and Health Study (2002–2006). Cadmium, PCBs, dioxins, p,p′-DDE and HCB were analysed in cord blood/plasma. When the child reached 7–9 years, height, weight, waist circumference and skinfolds were measured. Significant associations between prenatal exposure to EDCs and indicators of body composition were only found in girls. After adjustment for confounders and covariates, a significant negative association was found in girls between prenatal cadmium exposure and weight, BMI and waist circumference (indicator of abdominal fat) and the sum of four skinfolds (indicator of subcutaneous fat). In contrast, a significant positive association (after adjustment for confounders/covariates) was found between prenatal p,p′-DDE exposure and waist circumference as well as waist/height ratio in girls (indicators of abdominal fat). No significant associations were found for prenatal PCBs, dioxins and HCB exposure after adjustment for confounders/covariates. This study suggests a positive association between prenatal p,p′-DDE exposure and indicators of abdominal fat and a negative association between prenatal cadmium exposure and indicators of both abdominal as well as subcutaneous fat in girls between 7 and 9 years old.

A harmonized human biomonitoring pilot study was set up within the frame of the European projects DEMOCOPHES and COPHES. In 17 European countries, biomarkers of some environmental pollutants, including urinary cadmium and hair mercury, were measured in children and their mothers in order to obtain European-wide comparison values on these chemicals. The Belgian participant population consisted in 129 school children (6–11 years) and their mothers (≤ 45 years) living in urban or rural areas of Belgium. The geometric mean levels for mercury in hair were 0.383 μg/g and 0.204 μg/g for respectively mothers and children. Cadmium in mother's and children's urine was detected at a geometric mean concentration of respectively 0.21 and 0.04 μg/l. For both biomarkers, levels measured in the mothers and their child were correlated. While the urinary cadmium levels increased with age, no trend was found for hair mercury content, except the fact that mothers hold higher levels than children. The hair mercury content increased significantly with the number of dental amalgam fillings, explaining partially the higher levels in the mothers by their higher presence rate of these amalgams compared to children. Fish or seafood consumption was the other main parameter determining the mercury levels in hair. No relationship was found between smoking status and cadmium or mercury levels, but the studied population included very few smokers. Urinary cadmium levels were higher in both mothers and children living in urban areas, while for mercury this difference was only significant for children. Our small population showed urinary cadmium and hair mercury levels lower than the health based guidelines suggested by the WHO or the JECFA (Joint FAO/WHO Expert Committee on Food Additives). Only 1% had cadmium level slightly higher than the German HBM-I value (1 μg/l for adults), and 9% exceeded the 1 μg mercury/g hair suggested by the US EPA.

Sex hormone levels and timing of sexual maturation are considered important markers for health status of adolescents in puberty, and previous research suggests they might be influenced by metal exposure. In three campaigns of the Flemish Environment and Health Study (FLEHS I 2002–2006; FLEHS II 2007–2011 and FLEHS III 2012–2015), data were collected on internal exposure to metals (Cd, Cu, Pb, Cr, Mn, Tl, Ni, Sb, Hg, As and As species) and sexual maturation in 2671 14–15 years old adolescents. All metals were measured in blood and/or urine, except total- and methylmercury which were measured in hair samples. Sex hormone levels were measured in blood serum of adolescent males of the cohorts of FLEHS I and FLESH II. The use of a uniform methodology in successive campaigns allows to confirm associations between exposure and health in different cohorts and over time. Furthermore, mathematical and statistical density correction methods using creatinine or specific gravity were tested for urinary markers.Significant associations between sex hormones and maturity markers were observed in the FLEHS I and II campaigns, when both were assessed together. Regardless of the applied correction method, creatinine correction systematically introduced bias due to associations of creatinine with sex hormones and maturation markers, especially in adolescent males, while this is not the case for specific gravity. A series of exposure-response associations were found, but several involving Cd, Pb, As, Tl and Cu persisted in different FLEHS campaigns. The effects of Pb and Cu on luteinizing hormone, (free) testosterone, (free) oestradiol and maturation support a xenoestrogenic agonistic action on the feedback of oestradiol to the hypothalamus-pituitary-gonadal axis.Our results suggest that specific care should be taken when selecting urine density correction for investigating associations with hormonal and maturation markers in adolescent males. Furthermore, the possibility of xenoestrogenic effects of certain metals in environmentally exposed adolescents warrants further investigation. Keywords: FLEHS, Xenoestrogen, Exposure-response, Creatinine, Multiple regression, Metals

Background: Phthalates are chemicals which are widespread in the environment. Although the impacts on health of such exposure are unclear, there is evidence of a possible impact on the incidence of a diverse range of diseases. Monitoring of human exposure to phthalates is therefore important. This study aimed to determine the extent of phthalate exposure among mothers and their children in both rural and urban areas in Ireland, and to identify factors associated with elevated concentrations. It formed part of the 'Demonstration of a study to Co-ordinate and Perform Human Biomonitoring on a European Scale' (DEMOCOPHES) pilot biomonitoring study. Methods: the concentration of phthalate metabolites were determined from a convenience sample of 120 mother/child pairs. The median age of the children was 8 years. A questionnaire was used to collect information regarding lifestyle and environmental conditions of the children and mothers. Rigorous quality assurance within DEMOCOPHES guaranteed the accuracy and international comparability of results. Results: Phthalate metabolites were detected in all of the samples from both children and mothers. Concentrations were significantly higher in respondents from families with lower educational attainment and in those exposed to such items as polyvinyl chloride (PVC), fast food and personal care products (PCP). Conclusions: The study demonstrates that human biomonitoring for assessing exposure to phthalates can be undertaken in Ireland and that the exposure of the population is widespread. Further work will be necessary before the consequences of this exposure are understood. We would like to acknowledge the funders of the DEMOCOPHES project (LIFE09 ENV/BE/000410) which was jointly financed by the European Commission Programme LIFE and each participating country (http://www.eu-hbm.info/democophes/project-partners). In addition, we would like to thank the COPHES project for providing the operational and scientific framework (European Community’s Seventh Framework Programme—DG Research Grant Agreement Number 244237). Special thanks to all the mothers and children who agreed to participate in the study. In addition the WP team leaders and the national implementation teams, particularly the Irish national team (Catherine Cosgrove, David O’Brien, Rita O’Grady, Niamh McGrath, Anita Larini, Carol Nolan, Gemma McGrane and Sarah Duffy) for support in terms of data collection, analysis, and interpretation. We would like to thank Claire Dunne and Fiona Kavanagh for proof reading and assistance throughout the project, and Padraig Manning, Clinical Librarian and Elaine Scanlon, Library assistant from the HSE library in Steevens’ hospital, Dublin 8 for their assistance in accessing the literature. Sí

Early life exposure to endocrine disrupting chemicals (EDCs) has been frequently associated with impaired perinatal growth, an important risk factor for later onset of metabolic disorders. We analyzed whether the cord blood transcriptome showed early indications of alterations in metabolic processes in 195 human samples in relation to cord blood levels of dichlorodiphenyldichloroethylene (p,p′-DDE), polychlorinated biphenyl-153 (PCB-153), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonate (PFOS). Overall, 39 metabolically relevant transcription factors were significantly enriched (31 by p,p′-DDE, 10 by PCB-153, 8 by PFOA, and 2 by PFOS). These included the glucocorticoid receptor (p,p′-DDE and PCB-153) and the progesterone receptor (PFOA and PFOS). The ‘insulin receptor signaling’, ‘acute phase response signaling’, ‘Interleukin(IL)-6 signaling’, and ‘prolactin signaling’ pathways were significantly enriched in relation to p,p′-DDE. Transcriptional changes at birth suggest a role for specific metabolic targets as a link between prenatal EDC exposure and metabolic disorders later in life. © 2016 Elsevier Inc.

Introduction: Exposure to environmental pollutants might affect placental functioning and thus also fetal growth. Placental mitochondrial DNA (mtDNA) content can be indicative of oxidative damage t...

Background In Belgium, around 8.5% of the children have asthmatic symptoms. Increased asthma risk in children has been reported in relation to exposure to phthalate plasticizers but the underlying mechanisms are largely unknown. Aim The aim of this study was to identify if oxidative stress, assessed by excision of 8-hydroxydeoxyguanosine (8-OHdG) from damaged DNA, is an intermediate marker for the association between phthalate exposure and doctor-diagnosed asthma. Material and methods In 418 14–15-year-old youngsters, recruited as a representative sample of residents of Flanders (Belgium), personal exposure to phthalates was assessed by measuring phthalate metabolites in urine: mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-n-butyl phthalate (MnBP), mono-benzyl phthalate (MBzP), mono-isobutyl phthalate (MiBP) and mono-ethyl phthalate (MEP). Analysis of 8-OHdG in urine was used as a sensitive biomarker of oxidative stress at the level of DNA. The presence of doctor-diagnosed asthma was elicited by a self-administered questionnaire. Associations were assessed using multiple linear and logistic regression models. Mediation was tested using Baron and Kenny's regression approach. Results A significant increased risk of a youngster being diagnosed with asthma was found for both urinary MnBP (metabolite of dibutyl phthalate (DBP)) and the sum of the three di(2-ethylhexyl) phthalate metabolites (ΣDEHP = MEHP + MEHHP + MEOHP), with respective odds ratio of 1.84 [95% CI: 1.02, 3.32] for MnBP and 1.94 [95% CI: 1.07, 3.51] for ΣDEHP. In addition, we observed significant associations between all urinary phthalate metabolites and increased urinary levels of 8-OHdG. The associations were stronger in girls than in boys. We did not found evidence that 8-OHdG was associated with doctor-diagnosed asthma. Conclusion The results of our study are in line with other findings from epidemiological surveys and raise further concern about DEHP and DBP as risk factors for asthma, however, the underlying mechanisms are not yet well understood.

The aim of this study was to investigate the influence of the vertical position of a motorway on the pollutant concentrations in the vicinity of the motorway. Therefore, a near-road monitoring campaign was performed along two adjoining motorway stretches: one motorway at ground level and a motorway flyover. PM 2.5 and nitrogen oxides (NO, NO 2 and NO x ) were measured at both sides of the motorway on a 30-min resolution. In addition, EC (elemental carbon) was measured on both sides of the road on a daily basis using low volume samplers and thermal–optical transmission (TOT) analysis of filters. PNC (particle number concentration) was measured at one side. The measurement locations on each side of the road were located at 29 m and 102 m from the motorway at ground level and at 60 m and 120 m from the motorway flyover. Pollution roses, showed increased average concentrations in the direction of the road for nitrogen oxides and PM 2.5 . The impact of road traffic appeared to be higher at ground level compared to the flyover. The difference in concentration between both sides of the road for PM 2.5 , NO, NO 2 and NO x was analysed using linear mixed models. The concentration difference, which can be seen as the contribution of road traffic to the pollutant concentration, was calculated taking into account prevailing wind directions. The results indicate that taking into account confounding parameters (time of day, day of the week, distance to the road and wind speed), the contribution of the motorway traffic to pollutant concentrations is significantly higher when the motorway is at ground level. Furthermore, time of day and day of the week also have a significant effect on the concentration difference. The linear mixed model estimated a reduced road increment at the motorway flyover compared to the ground level motorway of 119 ppb for NO, 29 ppb for NO 2 and 3.5 μg m −3 for PM 2.5 . taking into account confounding parameters. The highest EC and PNC concentrations were measured downwind of the motorway at ground level.

An increasing number of studies have addressed the concern that environmental pollutants may contribute to the early origin of diseases. Epidemiologic studies suggest that prenatal exposure to air pollutants, several food contaminants, and chemicals present in consumer products are associated with nongenetically transmitted adverse health effects, which manifest after birth. Changes in neurobehavior, sexual development, the prevalence of asthma and allergy, and growth curves have been shown to be associated with pollutant exposure at early life stages. This review focuses on human molecular epidemiologic studies that contribute knowledge by introducing biomarker measurements to obtain a mechanistic understanding of the relation between early life exposures and health outcome. It has been hypothesized that subtle effects induced by pollutant exposure during development can lead to functional deficits and altered programming, which leads to increased disease or dysfunction risk later in life. Biomarker analysis may provide sensitive tools to trace these subtle changes and obtain mechanistic insight about the causal pathway between external exposure and health effects in human population studies. Biomarkers of exposure can be measured in mothers before conception, during pregnancy, or after birth. Different biological tissuessuch as peripheral or cord blood samples, hair samples, meconium, and urineprovide specific information that reflects the actual dose during pregnancy or at birth. Biomarkers of effect may include changes in hormone concentrations, oxidative stress variables, changes in gene expression levels, and epigenetic changes.

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

Research on the environment, health, and well-being nexus (EHWB) is shifting from a silo toward a systemic approach that includes the socio-economic context. To disentangle further the complex interplay between the socio-exposome and internal chemical exposure, we performed a meta-analysis of human biomonitoring (HBM) studies with internal exposure data on per-and polyfluoroalkyl substances (PFASs) and detailed information on risk factors, including descriptors of socio-economic status (SES) of the study population. PFASs are persistent in nature, and some have endocrine-disrupting properties. Individual studies have shown that HBM biomarker concentrations of PFASs generally increase with SES indicators, e.g., for income. Based on a meta-analysis (five studies) of the associations between PFASs and SES indicators, the magnitude of the association could be estimated. For the SES indicator income, changes in income were expressed by a factor change, which was corrected by the Gini coefficient to take into account the differences in income categories between studies, and the income range between countries. For the SES indicator education, we had to conclude that descriptors (&lt, college, x years of study, etc.) differed too widely between studies to perform a meta-analysis. Therefore, the use of the uniform ISCED (International Standard Classification of Education) is recommended in future studies. The meta-analysis showed that a higher income is associated with a higher internal exposure to PFASs (PFOS or perfluorooctanesulfonic acid, PFOA or perfluorooctanoic acid, PFNA or perfluorononanoic acid, PFHxS or perfluorohexane sulfonate). This is opposite to the environmental justice hypothesis, referring to an inequitable distribution of detrimental environmental effects toward poor and minority communities by a practice or policy. With a doubling of the income, internal exposure increased on average by 10%&ndash, 14%. Possible explanations for this difference are given, e.g., underlying differences in diet. However, other sources can also contribute, and the exact causes of SES-related differences in PFAS concentrations remain unclear. Studies are needed that include social descriptors together with lifestyle and dietary information as explanatory variables for internal chemical exposure levels. This will help clarify the underlying factors that link SES with inequity to environmental exposures, and will raise awareness and knowledge to strengthen the capacities of people and communities to advocate chemical exposure reduction in order to reduce this health inequity.

Cite this as: K. Bloemen, R. Van Den Heuvel, E. Govarts, J. Hooyberghs, V. Nelen, E. Witters, K. Desager and G. Schoeters, Clinical & Experimental Allergy, 2011 (41) 346–356. Summary Background Asthma is a complex clinical disease characterized by airway inflammation. Recently, various studies reported on the analysis of exhaled breath condensate (EBC) in the search for potential biomarkers for asthma. However, in a complex disease such as asthma, one biomarker might not be enough for early diagnosis or follow-up. Objective The use of proteome analysis may reveal disease-specific proteolytic peptide or protein patterns, and may lead to the identification of novel proteins for the detection of asthma. Methods Liquid chromatography and mass spectrometry were used to separate and detect proteins (proteolytic peptides) present in EBC samples from 30 healthy children and 40 children with asthma in the age group of 6–12 years. Results Support vector machine analysis resulted in differentiating profiles based on asthma status. These proteolytic peptide patterns were not correlated to some well known (spirometry, exhaled nitric oxide) and more recently described exhaled markers (EBC pH, LTB4). The more abundant proteins in EBC were identified as cytokeratins, albumin, actin, haemoglobin, lysozyme, dermcidin, and calgranulin B. Conclusion Although the exact role in the disease development or physiological state of the airways of the proteins described in the presented pattern is not clear at this moment, this is an important step in the search for exhaled biomarkers for asthma. This study shows that EBC contains proteins that are of interest for future non-invasive asthma diagnosis or follow-up.

Regression tree analysis, a non-parametric method, was undertaken to identify predictors of the serum concentration of polychlorinated biphenyls (sum of marker PCB1 138, 153, and 180) in humans. This method was applied on biomonitoring data of the Flemish Environment and Health study (2002-2006) and included 1679 adolescents and 1583 adults. Potential predictor variables were collected via a self-administered questionnaire, assessing information on lifestyle, food intake, use of tobacco and alcohol, residence history, health, education, hobbies, and occupation. Relevant predictors of human PCB exposure were identified with regression tree analysis using ln-transformed sum of PCBs, separately in adolescents and adults. The obtained results were compared with those from a standard linear regression approach. The results of the non-parametric analysis confirm the selection of the covariates in the multiple regression models. In both analyses, blood fat, gender, age, body-mass index (BMI) or change in bodyweight, former breast-feeding, and a number of nutritional factors were identified as statistically significant predictors in the serum PCB concentration, either in adolescents, in adults or in both. Regression trees can be used as an explorative analysis in combination with multiple linear regression models, where relationships between the determinants and the biomarkers can be quantified.

Notwithstanding evidence is present that physicochemical characteristics of ambient particles attribute to adverse health effects, there is still some lack of understanding in this complex relationship. At this moment it is not clear which properties (such as particle size, chemical composition) or sources of the particles are most relevant for health effects. This study investigates the in vitro toxicity of PM10, in relation to PM chemical composition, black carbon (BC), endotoxin content and oxidative potential (OP). In 2013-2014 PM10 was sampled (24 h sampling, 108 sampling days) in ambient air at three sites in Flanders (Belgium) with different pollution characteristics: an urban traffic site (Borgerhout), an industrial area (Zelzate) and a rural background location (Houtem). To characterize the toxic potential of PM10, airway epithelial cells (Beas-2B cells) have been exposed to particles in vitro. Different endpoints were studied including cell damage and death (cell viability) using the Neutral red Uptake assay, the production of pro-inflammatory molecules by interleukin 8 (IL-8) induction and DNA-damaging activity using the FPG-modified Comet assay. The endotoxin levels in the collected samples were analysed and the capacity of PM10 particles to produce reactive oxygen species (OP) was evaluated by electron paramagnetic resonance (EPR) spectroscopy. Chemical characteristics of PM10 (BC, As, Cd, Cr, Cu, Mn, Ni, Pb, Zn) and meteorological conditions were recorded on the sampling days. PM10 particles exhibited dose-dependent cytotoxicity in Beas-2B cells and were found to significantly induce the release of IL-8 in samples from the three locations. Oxidatively damaged DNA was observed in exposed Beas-2B cells. Endotoxin levels above the detection limit were detected in half of the samples. OP was measurable in all samples. Associations between PM10 characteristics and biological effects of PM10 were assessed by single and multiple regression analyses. The reduction in cell viability was significantly correlated with BC, Cd and Pb. The induction of IL-8 in Beas-2B cells was significantly associated with Cu, Ni and Zn and endotoxin. Endotoxin levels explained 33% of the variance in IL-8 induction. A significant interaction between ambient temperature and endotoxin on the pro-inflammatory activity was seen. No association was found between OP and the cellular responses. This study supports the hypothesis that, on an equal mass basis, PM10 induced biological effects differ due to differences in PM10 characteristics. Metals (Cd, Cu, Ni and Zn), BC, and endotoxin were among the main determinants for the observed biological responses. (c) 2016 Elsevier Inc. All rights reserved.

Copyright © 2015 by the Endocrine Society. Context: Obesityanddiabetes are epidemic in the European Union(EU). Exposure to endocrine-disrupting chemicals (EDCs) is increasingly recognized as a contributor, independent of diet and physical activity. Objective: The objective was to estimate obesity, diabetes, and associated costs that can be reasonably attributed to EDC exposures in the EU. Design: An expert panel evaluated evidence for probability of causation using weight-of-evidence characterization adapted from that applied by the Intergovernmental Panel on Climate Change. Exposureresponse relationships and reference levels were evaluated for relevant EDCs, and biomarker data were organized from peer-reviewed studies to represent European exposure and burden of disease. Cost estimationas of2010utilized published cost estimates for childhood obesity, adult obesity, and adult diabetes. Setting, Patients and Participants, and Intervention: Cost estimation was performed from the societal perspective. Results: The panel identified a 40% to 69% probability of dichlorodiphenyldichloroethylene causing 1555 cases of overweight atage10 (sensitivity analysis: 1555-5463) in 2010 with associated costs of£24.6 million (sensitivity analysis:£24.6-86.4 million). A 20% to 39% probability was identified for dichlorodiphenyldichloroethylene causing 28 200 cases of adult diabetes (sensitivity analysis: 28 200-56 400) with associated costs of£835million (sensitivity analysis:£835million-16.6 billion).Thepanel also identifieda40%to69% probability of phthalate exposure causing 53 900 cases of obesity in older women and £15.6 billion in associated costs. Phthalate exposure was also found to have a 40% to 69% probability of causing 20 500 new-onset cases of diabetes in older women with £607 million in associated costs. Prenatal bisphenol A exposure was identified to have a 20% to 69% probability of causing 42 400 cases of childhoodobesity, with associated lifetime costs of £1.54 billion. Conclusions: EDC exposures in the EU contribute substantially to obesity and diabetes, with a moderate probability of >£18 billion costs per year. This is a conservative estimate; the results emphasize the need to control EDC exposures.

Prenatal chemical exposure has been frequently associated with reduced fetal growth by single pollutant regression models although inconsistent results have been obtained. Our study estimated the effects of exposure to single pollutants and mixtures on birth weight in 248 mother-child pairs. Arsenic, copper, lead, manganese and thallium were measured in cord blood, cadmium in maternal blood, methylmercury in maternal hair, and five organochlorines, two perfluorinated compounds and diethylhexyl phthalate metabolites in cord plasma. Daily exposure to particulate matter was modeled and averaged over the duration of gestation. In single pollutant models, arsenic was significantly associated with reduced birth weight. The effect estimate increased when including cadmium, and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) co-exposure. Combining exposures by principal component analysis generated an exposure factor loaded by cadmium and arsenic that was associated with reduced birth weight. MECPP induced gender specific effects. In girls, the effect estimate was doubled with co-exposure of thallium, PFOS, lead, cadmium, manganese, and mercury, while in boys, the mixture of MECPP with cadmium showed the strongest association with birth weight. In conclusion, birth weight was consistently inversely associated with exposure to pollutant mixtures. Chemicals not showing significant associations at single pollutant level contributed to stronger effects when analyzed as mixtures.

Background Dioxins and dioxin-like compounds are endocrine disrupting chemicals (EDCs). Experimental studies suggest perinatal exposure to EDCs results in later obesity. However, the few epidemiological investigations on dioxins are inconclusive. We investigated perinatal exposure to dioxins and dioxin-like compounds, infant growth and body mass index (BMI) in childhood. Methods We pooled data from 3 European birth cohorts (Belgian, Norwegian, Slovak) with exposure assessment in cord blood or breast milk. Two cohorts had dioxin-like toxicity assessed using dioxin-responsive chemical-activated luciferase expression (DR-CALUX) bioassay and one cohort had measured concentrations of dioxins, furans and dioxin-like polychlorinated biphenols with CALUX relative potency values applied. Growth was cohort- and sex-specific change in weight-for-age z-score between birth and 24 months (N = 367). BMI was calculated at around 7 years (median 7.17, interquartile range [IQR] 7.00–7.37 years, N = 251), and overweight defined according to international standards for children equivalent to adult BMI > 25 kg/m2 (Cole and Lobstein, 2012). We fitted multivariate models using generalized estimating equations, and tested effect modification by sex, breastfeeding and cohort. Results per 10 pg CALUX TEQ/g lipid increase in exposure. Results Dioxin exposure was highest in the Belgian and lowest in the Norwegian cohort; median (IQR) of the pooled sample 13 (12.0) pg CALUX TEQ/g lipid. Perinatal exposure to dioxins and dioxin-like compounds appeared associated with increased growth between 0 and 24 months (adjusted estimate for change in z-score: β = 0.07, 95% CI: − 0.01, 0.14). At 7 years, dioxins exposure was associated with a statistically significant increase in BMI in girls (adjusted estimate for BMI units β = 0.49, 95% CI: 0.07, 0.91) but not in boys (β = − 0.03, 95% CI: − 0.55, 0.49) (p-interaction = 0.044). Furthermore, girls had a 54% (− 6%, 151%) increased risk of overweight at 7 years (p-interaction = 0.023). Conclusion Perinatal exposure to dioxin and dioxin-like compounds was associated with increased early infant growth, and increased BMI in school age girls. Studies in larger sample sizes are required to confirm these sex-specific effects. © 2016 Elsevier Ltd Background Dioxins and dioxin-like compounds are endocrine disrupting chemicals (EDCs). Experimental studies suggest perinatal exposure to EDCs results in later obesity. However, the few epidemiological investigations on dioxins are inconclusive. We investigated perinatal exposure to dioxins and dioxin-like compounds, infant growth and body mass index (BMI) in childhood. Methods We pooled data from 3 European birth cohorts (Belgian, Norwegian, Slovak) with exposure assessment in cord blood or breast milk. Two cohorts had dioxin-like toxicity assessed using dioxin-responsive chemical-activated luciferase expression (DR-CALUX) bioassay and one cohort had measured concentrations of dioxins, furans and dioxin-like polychlorinated biphenols with CALUX relative potency values applied. Growth was cohort- and sex-specific change in weight-for-age z-score between birth and 24 months (N = 367). BMI was calculated at around 7 years (median 7.17, interquartile range [IQR] 7.00–7.37 years, N = 251), and overweight defined according to international standards for children equivalent to adult BMI > 25 kg/m 2 (Cole and Lobstein, 2012). We fitted multivariate models using generalized estimating equations, and tested effect modification by sex, breastfeeding and cohort. Results per 10 pg CALUX TEQ/g lipid increase in exposure. Results Dioxin exposure was highest in the Belgian and lowest in the Norwegian cohort; median (IQR) of the pooled sample 13 (12.0) pg CALUX TEQ/g lipid. Perinatal exposure to dioxins and dioxin-like compounds appeared associated with increased growth between 0 and 24 months (adjusted estimate for change in z-score: β = 0.07, 95% CI: − 0.01, 0.14). At 7 years, dioxins exposure was associated with a statistically significant increase in BMI in girls (adjusted estimate for BMI units β = 0.49, 95% CI: 0.07, 0.91) but not in boys (β = − 0.03, 95% CI: − 0.55, 0.49) (p-interaction = 0.044). Furthermore, girls had a 54% (− 6%, 151%) increased risk of overweight at 7 years (p-interaction = 0.023). Conclusion Perinatal exposure to dioxin and dioxin-like compounds was associated with increased early infant growth, and increased BMI in school age girls. Studies in larger sample sizes are required to confirm these sex-specific effects.

© 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.

'Reproduced with permission from Environmental Health Perspectives', Background: For Europe as a whole, data on internal exposure to environmental chemicals do not yet exist. Characterization of the internal individual chemical environment is expected to enhance understanding of the environmental threats to health. Objectives: We developed and applied a harmonized protocol to collect comparable human biomonitoring data all over Europe. Methods: In 17 European countries, we measured mercury in hair and cotinine, phthalate metabolites, and cadmium in urine of 1,844 children (5–11 years of age) and their mothers. Specimens were collected over a 5-month period in 2011–2012. We obtained information on personal characteristics, environment, and lifestyle. We used the resulting database to compare concentrations of exposure biomarkers within Europe, to identify determinants of exposure, and to compare exposure biomarkers with healthbased guidelines. Results: Biomarker concentrations showed a wide variability in the European population. However, levels in children and mothers were highly correlated. Most biomarker concentrations were below the health-based guidance values. Conclusions: We have taken the first steps to assess personal chemical exposures in Europe as a whole. Key success factors were the harmonized protocol development, intensive training and capacity building for field work, chemical analysis and communication, as well as stringent quality control programs for chemical and data analysis. Our project demonstrates the feasibility of a Europe-wide human biomonitoring framework to support the decision-making process of environmental measures to protect public health., The research leading to these results received funding for the COPHES project (COnsortium to Perform Human biomonitoring on a European Scale) from the European Community’s Seventh Framework Programme [FP7/2007–2013] under grant agreement 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. For information on both projects as well as on the national co-funding institutions, see http://www.eu-hbm.info/. The sponsors had no role in the study design, data collection, data analysis, data interpretation or writing of the report.

Within the Flemish Environment and Health stud- ies (FLEHS I, 2002-2006, and FLEHS II, 2007-2012), pes- ticide exposure, hormone levels and degree of sexual matura- tion were measured in 14-15-year-old adolescents residing in Flanders (Belgium). In FLEHS II, geometric mean concentra- tions (with 95 % confidence interval (CI)) of 307 (277-341) and 36.5 ng L �1 (34.0-39.2) were found for p,p'- dichlorophenyldichloroethylene (p,p'-DDE) and hexachlorobenzene (HCB). These values were respectively 26 and 60 % lower than levels in FLEHS I, 5 years earlier. Metabolites of organophosphorus pesticides (OPPs) and of para-dichlorobenzene were measured for the first time in FLEHS II, yielding concentrations of 11.4, 3.27 and 1.57 μ gL �1 for the sum of dimethyl- and diethyl phosphate metabolites and 2,5-dichlorophenol (2,5-DCP), respectively. Data on internal exposure of HCB showed a positive correla- tion with sexual maturation, testosterone and the aromatase index for boys and with free thyroxine (fT4) and thyroid stimulating hormone (TSH) (both boys and girls). For both p,p'-DDE and HCB, a negative association with sexual devel- opment in girls was found. The OPP metabolites were nega- tively associated with sex hormone levels in the blood of boys and with sexual maturation (both boys and girls). The pesti- cide metabolite 2,5-DCP was negatively correlated with free T4, while a positive association with TSH was reported (boys and girls). These results show that even exposure to relatively low concentrations of pesticides can have significant influ- ences on hormone levels and the degree of sexual maturation in 14-15-year-old adolescents.

© 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.

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

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

Verner et al. (2013) recently questioned whether the association between cord levels of PCB-153 (polychlorinated biphenyl-153) and birth weight reported in our recent meta-analysis (Govarts et al. 2012) might be attributable to the influence of gestational weight gain (GWG), a factor that may be related to both PCB-153 concentrations and birth weight. By using simulated data in a physiologically based pharmacokinetic (PBPK) model, Verner et al. (2013) concluded that The association between prenatal levels of PCBs and birth weight may be strongly confounded by the effect of [GWG] on both blood PCB levels and birth weight. In our recently published meta-analysis (Govarts et al. 2012), the influence of weight gain was considered only in a sensitivity analysis because we did not have this information from many cohorts at that time. Since the publication of that article, we have obtained more individual-level data on GWG for a number of the cohorts, allowing us to repeat these analyses to further assess such influence. Seven of the 12 birth cohorts that participated in our previous meta-analysis (Govarts et al. 2012) had data on GWG available, for a total of 4,473 mother–child pairs. GWG data from 3 cohorts was extracted from prenatal records, whereas for the other cohorts the classification was based on mother’s recall. In most cohorts, weight in late pregnancy was obtained at birth or at some weeks before delivery, but in two cohorts these data were obtained some years after birth. In two cohorts, both measured and self-reported data on mother’s weight was available, and an excellent correlation was observed (Spearman r = 0.95; p < 0.001). In the present reanalysis of the data, we also estimated the changes in fat mass (FM) as a function of GWG (Butte et al. 2003). Spearman correlation coefficients were calculated between PCB-153 and GWG/FM and between GWG/FM and birth weight. We first estimated the association between cord serum PCB-153 and birth weight using linear multivariate-adjusted regression models in each cohort separately, and then we used mixed-effect models to estimate the combined effect (pooled analysis). We included absolute GWG or estimated FM as additional potential confounders in the models. The absolute GWG and estimated FM distributions were relatively similar among cohorts (mean + SD was 13.9 ± 5.3 kg for GWG and 5.5 ± 4.5 kg for FM). We found low correlations between PCB-153 and GWG/FM and between GWG/FM and birth weight (r < 0.18). The effect estimate of the combined analysis yielded a negative association between PCB-153 and birth weight equivalent to a 293-g reduction [95% confidence interval (CI): –536, –50] in birth weight per 1-µg/L increase in cord serum PCB-153. After including absolute GWG or estimated FM in the model, the strength of the association was reduced by 48% [–153 g (95% CI: –340, 30)] and 31% [–204 g (95% CI: –411, 0)], respectively. Our reanalysis of earlier data with some new data confirms that GWG may indeed confound the relationship between PCB-153 and birth weight; however, when we included in the model either absolute GWG or estimated FM, which is a more precise estimate of maternal lipid gain (Butte et al. 2003), we still observed an important reduction in birth weight as PCB-153 levels increased. We cannot exclude the possibility of residual confounding due to potential measurement error of GWG, which may further reduce the effect toward the null. However, two of the included cohorts showed high correlations between measured and self-reported weight, suggesting that misclassification due to maternal weight reports is likely to be small and negligible. Misclassification could result from inaccurate assessment of FM. In a recent study, Maple-Brown et al. (2013) observed that maternal age and prepregnancy body mass index can be related to an increase in gestational FM, suggesting that it is worth considering both of them in models assessing fat mass. As suggested by Verner et al. (2013), we have considered GWG as a potential confounder because it increases the volume of lipids diluting PCB levels in blood (Glynn et al. 2011) and increases birth weight of the offspring (Siega-Riz et al. 2009). However, other than a confounding factor, GWG could be an intermediate factor on a causal path between PCB-153 exposure and birth weight. If this is the case, then controlling for GWG in the models would lead to an overadjustment bias (Schisterman et al. 2009) in the effect estimates and would be inappropriate if the main aim is to estimate the total (and not the direct) effect of PCB-153 on birth weight. In conclusion, in interpreting the findings by Verner et al. (2013) one should take into account that PBPK models, although useful, are based on many assumptions. The only way to verify them is through testing in population-based studies. Our analysis clearly indicates that attributing all the effect of PCBs on birth weight to GWG appears an oversimplification.

International audience; BACKGROUND: Persistent organic pollutants may affect the immune and respiratory systems, but available evidence is based on small study populations. We studied the association between prenatal exposure to dichlorodiphenyldichloroethylene (DDE) and polychlorinated biphenyl 153 (PCB 153) and children's respiratory health in European birth cohorts. METHODS: We included 4608 mothers and children enrolled in 10 birth cohort studies from 7 European countries. Outcomes were parent-reported bronchitis and wheeze in the first 4 years of life. For each cohort, we performed Poisson regression analyses, modeling occurrences of the outcomes on the estimates of cord-serum concentrations of PCB 153 and DDE as continuous variables (per doubling exposure) and as cohort-specific tertiles. Summary estimates were obtained through random-effects meta-analyses. RESULTS: The risk of bronchitis or wheeze (combined variable) assessed before 18 months of age increased with increasing DDE exposure (relative risk [RR] per doubling exposure = 1.03 [95% confidence interval = 1.00-1.07]). When these outcomes were analyzed separately, associations appeared stronger for bronchitis. We also found an association between increasing PCB 153 exposure and bronchitis in this period (RR per doubling exposure = 1.06 [1.01-1.12]) but not between PCB 153 and wheeze. No associations were found between either DDE or PCB 153 and ever-wheeze assessed after 18 months. Inclusion of both compounds in the models attenuated risk estimates for PCB 153 tertiles of exposure, whereas DDE associations were more robust. CONCLUSION: This large meta-analysis suggests that prenatal DDE exposure may be associated with respiratory health symptoms in young children (below 18 months), whereas prenatal PCB 153 levels were not associated with such symptoms.

Since the CALUX (Chemically Activated LUciferase gene eXpression) bioassay is a fast and inexpensive tool for the determination of dioxin-like compounds in a large number of samples and requires only small sample volumes, the use of this technique in human biomonitoring programs provides a good alternative to GC-HRMS. In this study, a new CALUX method for the separate analysis of PCDD/Fs and dioxin-like PCBs (dl-PCBs) in small amounts of human milk samples with the new sensitive H1L7.5c1 cell line was used to analyze 84 human milk samples, collected from mothers residing in the Flemish rural communities. The geometric mean CALUX-Bioanalytical Equivalent (CALUX-BEQ) values, reported for the 84 mothers from the study area were 10.4 (95% CI: 9.4-11.4) pg CALUX-BEQ per gram lipid or 0.41 (95% CI: 0.37-0.45) pg CALUX-BEQ per gram milk for the PCDD/Fs and 1.73 (1.57-1.91) pg CALUX-BEQ per gram lipid or 0.07 (95% CI: 0.06-0.08) pg CALUX-BEQ per gram milk for the dioxin-like PCBs. Multiple regression analysis showed significant associations between PCDD/Fs and weight change after pregnancy, smoking and consumption of local eggs. One pooled human milk sample was analyzed with both CALUX and GC-HRMS. The ratio of CALUX and GC-HRMS results for this sample were respectively 1.60, 0.58 and 1.23 for the PCDD/Fs, the dl-PCBs and the sum of both fractions, when using the 2005-TEF values. Additionally, also low levels of certain brominated dioxins and furans were detected in the pooled sample with GC-HRMS.

To collect information on the concentrations of persistent organic pollutants (POPs) in the rural areas in Flanders (Belgium), 84 breastfeeding mothers were recruited in rural communities in East and West Flanders and Flemish Brabant in 2009-2010. Polychlorinated biphenyl (PCB) congeners, organochlorine pesticides, brominated flame retardants, perfluorinated compounds, polychlorinated dibenzodioxines and dibenzofurans, and dioxin-like PCBs were measured in individual milk samples and in a pooled milk sample, while some additional pollutants were only measured in the pooled sample. For most pollutants, the concentrations in this study were lower or comparable to the concentrations measured in the pooled Belgian sample of the WHO human milk study of 2006, except for the pesticides dichlorodiphenyltrichloroethane DDT (+25% for Sigma DDT and metabolites) and trans-nonachlor (+94%), and for the brominated flame retardant hexachlorocyclododecane HBCD (+153%). Perfluorinated compounds were for the first time determined in human milk samples from Belgium and the concentrations were comparable to those from other European countries. Also, interesting associations were found between the concentrations of POPs measured in human milk and personal characteristics as well as dietary habits of the study population. PFOS en PFOA concentrations were significantly higher in milk of primiparous participants compared to mothers who gave birth to their second child. Lower brominated PBDE congeners increased with increasing BMI of the mothers (p = 0.01 for BDE 47, p = 0.02 for BDE 99 and p = 0.02 for BDE 100). Participants consuming milk or dairy products daily had significant higher concentrations of Sigma DDTs (p = 0.03) and oxychlordane (p = 0.047) in their human milk samples. (C) 2012 Elsevier Ltd. All rights reserved.

With the objective to evaluate exposure of the population in Flanders (Belgium) to perfluorinated compounds (PFCs), we measured perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) in settled dust in homes and offices, in a selection of food items from local origin, in drinking-water and in human serum. We complemented the data with results from a literature survey. Based on this dataset we calculated intake by children and adults from food, drinking-water, settled dust and soil, and air. Dietary exposure dominated overall intake. For adults, average dietary intake equalled 24.2 (P95 40.9) ng PFOS kg−1 d−1 and 6.1 (P95 9.6) ng PFOA kg−1 d−1, whereas for children the dietary intake was about 3 times higher. Predicted intake is high when compared to assessments in other countries, and to serum levels from Flanders, but comparable to the intakes published by The European Food Safety Authority (EFSA) in 2008. Intake of PFOS and PFOA remained below the Tolerable Daily Intake.

Asthma-related symptoms can manifest in children during the early years, but only some of the children will develop the disease. This feasibility study showed that it is possible to apply non-invasive markers (in urine, exhaled nitric oxide (FENO) and exhaled breath condensate (EBC)) in 3-year-old children, and evaluated the biomarkers in relation to health outcomes and potential modifiers. FENO was correlated with respiratory allergy, and was borderline significantly correlated with wheezing, but not with the asthma predictive index (mAPI). EBC pH and urinary 8-oxo-deoxyguanosine were not significantly correlated with these clinical outcomes. An EBC proteolytic peptide pattern was developed, which could distinguish between mAPI-positive and -negative children. Non-invasive biomarkers may become a promising tool for investigating respiratory health in children but further research is needed.

Human biomonitoring provides an integrated measure for individual exposure to environmental pollutants. Better insight in inter-individual variability of biomarkers of exposure may help in the interpretation of biomonitoring studies. The aim was to study the impact of outliers, determine the optimal unit for fat-soluble biomarkers in serum and quantify the major determinants for biomarkers of exposure to polychlorinated aromatic hydrocarbons (PCAHs) in three age groups. Data were obtained from the Flemish Environment and Health Study (2002-2006). Marker PCBs (sum of 138,153,180), hexachlorobenzene (HCB) and p,p'-DDE were measured in cord blood samples of 1196 newborns, in serum samples of 1679 adolescents (14-15 years) and 1583 adults (50-65 years). Exclusion of influential outliers in multiple linear regression models lead to models that are better applicable to the general population. In terms of adjusted R 2, the regression model with the pollutant expressed in volume-based units and blood fat as a separate independent variable was superior compared to models with other units. We found highly consistent relationships between the serum concentration of PCAHs and blood fat, age, changes in body weight, animal fat in the diet, local vegetable consumption (HCB and p,p'-DDE only) and being breastfed as a baby (in adolescents only). The impact of sex and BMI differed toy age. For biomarkers of persistent pollutants that reflect long-term exposure, the relation between the covariates and the biomarkers can be well quantified. (C) 2009 Elsevier Inc. All rights reserved.