Search

Background: Studies on cognitive and neurodevelopmental outcomes have shown inconsistent results regarding the association with prenatal exposure to perfluoroalkyl substance (PFAS) and organochlorines. Assessment of mixture effects of correlated chemical exposures that persist in later life may contribute to the unbiased evaluation and understanding of dose-response associations in real-life exposures., Methods: For a subset of the 4th Flemish Environment and Health Study (FLEHS), concentrations of four PFAS and six organochlorines were measured in respectively 99 and 153-160 cord plasma samples and 15 years later in adolescents' peripheral serum by Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS). Sustained and selective attention were measured at 14-15 years with the Continuous Performance Test (CPT) and Stroop Test as indicators of potential neurodevelopmental deficits. Quantile g-computation was applied to assess the joint associations between prenatal exposure to separate and combined groups of PFAS and organochlorines and performance in the CPT and Stroop Test at adolescence. Subsequently, individual effects of each chemical compound were analyzed in mixed effects models with two sets of covariates. Analytical data at birth and at the time of cognitive assessment allowed for off-setting postnatal exposure., Results: In mixtures analysis, a simultaneous one-quantile increase in the natural log-transformed values of PFAS and organochlorines combined was associated with a decrease in the mean reaction time (RT) and the reaction time variability (RTV) in the CPT (β = -15.54, 95% CI:-29.64, -1.45, and β = -7.82, 95% CI: -14.97, -0.67 respectively) and for the mixture of PFAS alone with RT (β = -11.94, 95% CI: -23.29, -0.60). In the single pollutant models, these results were confirmed for the association between perfluorohexanesulfonate (PFHxS) with RT (β = -17.95, 95% CI = -33.35, -2.69) and hexachlorobenzene with RTV in the CPT (β = -5.78, 95% CI: -10.39, -0.76). Furthermore, the participants with prenatal exposure above the limit of quantification for perfluorononanoic acid (PFNA) had a significantly shorter RT and RTV in the CPT (β = -23.38, 95% CI: -41.55, -5.94, and β = -9.54, 95% CI: -19.75, -0.43, respectively)., Conclusion: Higher prenatal exposure to a PFAS mixture and a mixture of PFAS and organochlorines combined was associated with better sustained and selective attention during adolescence. The associations seemed to be driven by PFHxS and were not linked to exposure levels at the time of assessment., (Copyright © 2024. Published by Elsevier GmbH.)

Human biomonitoring (HBM) monitors levels of environmental pollutants in human samples, which often is a topic of concern for residents near industrially contaminated sites (ICSs). Around an ICS area in Menen (Belgium), including a (former) municipal waste incinerator and a metal recovery plant, increasing environmental concentrations of dioxins and polychlorinated biphenyls (PCBs) were observed, causing growing concern among residents and authorities. The local community succeeded in convincing the responsible authorities to investigate the problem and offer research funding. Persistent organic pollutants (POPs) were measured in two consecutive HBM studies (2002-2006 and 2010-2011), in the context of the Flemish Environment and Health Study (FLEHS), as well as in soil and locally produced food. Meanwhile, local authorities discouraged consumption of locally produced food in a delineated area of higher exposure risk. Ultimately, HBM and environmental data enabled tailored dietary recommendations. This article demonstrates the usefulness of HBM in documenting the body burdens of residents near the ICS, identifying exposure routes, evaluating remediating actions and providing information for tailored policy strategies aiding to further exposure reduction. It also highlights the role of the local stakeholders as an example of community-based participatory research and how such an approach can create societal support for research and policy.

Background: We report data of a Belgian observational prospective cohort study regarding cognitive and behavioural development until the age of 36 months in relation to internal exposure to organochlorine pollutants [sum of polychlorinated biphenyls (sum PCB), dioxin-like activity, PCB118, PCB170, hexachlorobenzene (HCB) and p,p'-dichlorodiphenyldichloroethylene (DDE)] measured in cord blood., Methods: Participants were recruited as part of an Flemish Environmental Health Survey (2002-2006). Two hundred and six mother-child pairs were recruited. Hundred twenty five toddlers [Reynell Taal Ontwikkelings Schalen (language development, RTOS), Snijders-Oomen Niet-verbale intelligentietest (non-verbal intelligence, SON), Bayley Scales, milestones, Infant Behaviour Questionnaire (IBQ), gender specific play behaviour, Neurobehavioral Evaluation System (NES)-attentional task] and their mothers [Home Observation Measurement of the Environment (HOME), Wechsler Abbreviated Scale of Intelligence (WASI), State-Trait Anxiety Inventory (STAI), general questionnaires] were tested. Statistical analysis was performed with the SPSS program. Much attention was paid to confounding factors., Results: In the first years of development, higher organochlorine pollutants were associated with less active children (delayed crawling: sum PCB*HCB (p < 0.05), sumPCB*DDE (p < 0.1); delayed first steps alone: sum PCB (p < 0.5), PCB118 (p < 0.01), PCB170 (p < 0.01), HCB (p < 0.01); less switching between toys: sum PCB (p < 0.01); less switching between toys in boys: PCB118 (p < 0.01), sum PCB(p < 0.01)). At 12 months children with higher dioxin-like activity tended to show less fear responses(p < 0.1) (IBQ 12 months). At 36 months, a slower development of language comprehension (RTOS) was related to all organochlorine exposure parameters(p < 0.1 or p < 0.05) except DDE. Lower nonverbal IQ scores (SON) were related to PCB118 in boys only(p < 0.05 or p < 0.01). Less masculine and more non-gender specific play behaviour was associated with sum PCB in boys and girls at 36 months(p < 0.1). Moreover, PCB118 (p < 0.05), PCB170 (p < 0.1), HCB(p < 0.05) and DDE(p < 0.05) were associated with diminished masculine play behaviour in boys., Conclusion: Our data confirm the observations that neurobehavioral development of young children is adversely influenced by environmental concentrations of PCBs, especially in boys. In this context, observation of play behaviour seems to be a reliable, easy to perform and sensitive test to detect neurotoxic effects of chemicals like PCB's and dioxin-like compounds in very young children. On the basis of our results, we hypothesize that an underarrousal pattern may play a role in the spectrum of effects measured in toddlers prenatally exposed to PCBs and dioxin-like compounds.

Background and Aims: Prenatal chemical exposure has frequently been associated with reduced fetal growth although results have been inconsistent. Most studies associate single pollutant exposure to this health outcome, even though this does not reflect real life situations as humans are exposed to many pollutants during their life time. The objective of this study is to investigate the association between prenatal exposure to a mixture of persistent environmental chemicals and birth weight using multipollutant models., Methods: We combined exposure biomarker data measured in cord blood samples of 1579 women from four Flemish birth cohorts collected over a 10 years' time period. The common set of available and detectable exposure measures in these cohorts are three polychlorinated biphenyls (PCB) congeners (138, 153 and 180), hexachlorobenzene (HCB), dichlorodiphenyldichloroethylene (p,p'-DDE) and the metals cadmium and lead. Multiple linear regression (MLR), Bayesian Information Criterion (BIC), penalized regression using minimax concave penalty (MCP) and Bayesian Adaptive Sampling (BAS) were applied to assess the influence of multiple pollutants in a single analysis on birth weight, adjusted for a priori selected covariates., Results: In the pooled dataset, a median (P25-P75) birth weight and gestational age of 3420 (3140-3700) grams and 39 (39-40) weeks was observed respectively. The median contaminant levels in cord blood were: 15.8, 26.5, 18.0, 16.9 and 91.5 ng/g lipid for PCB 138, PCB 153, PCB 180, HCB and p,p'-DDE, respectively, 0.075 µg/L for cadmium and 9.7 µg/L for lead. According to the applied statistical methods for multipollutant assessment, p,p'-DDE and PCB 180 were most consistently associated with birth weight. In addition, PCB 153 was selected when applying MCP and BAS. An inverse association with birth weight was found for the PCB congeners, while an increased birth weight was observed for elevated levels of p,p'-DDE., Conclusions: Assessing the health risk of combinations of exposure biomarkers reflects better real-world situations and thereby allows more effective risk assessment. Our results add to the existing evidence based on detrimental effects of PCBs on birth weight and indicate a possible increase in birth weight due to p,p'-DDE (while correcting for PCBs)., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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 μg/L for PFOS and 2 μg/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., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Mitochondrial DNA (mtDNA) content and telomere length are putative aging biomarkers and are sensitive to environmental stressors, including pollutants. Our objective was to identify, from a set of environmental exposures, which exposure is associated with leukocyte mtDNA content and telomere length in adults. This study includes 175 adults from 50 to 65 years old from the cross-sectional Flemish Environment and Health study, of whom leukocyte telomere length and mtDNA content were determined using qPCR. The levels of exposure of seven metals, 11 organohalogens, and four perfluorinated compounds (PFHxS, PFNA, PFOA, PFOS) were measured. We performed sparse partial least-squares regression analyses followed by ordinary least-squares regression to assess the multipollutant associations. While accounting for possible confounders and coexposures, we identified that urinary cadmium (6.52%, 95% confidence interval, 1.06, 12.28), serum hexachlorobenzene (2.89%, 018, 5.68), and perfluorooctanesulfonic acid (11.38%, 5.97, 17.08) exposure were positively associated ( p < 0.05) with mtDNA content, while urinary copper (-9.88%, -14.82, -4.66) and serum perfluorohexanesulfonic acid (-4.75%, -8.79, -0.54) exposure were inversely associated with mtDNA content. Urinary antimony (2.69%, 0.45, 4.99) and mercury (1.91%, 0.42, 3.43) exposure were positively associated with leukocyte telomere length, while urinary copper (-3.52%, -6.60, -0.34) and serum perfluorooctanesulfonic acid (-3.64%, -6.60, -0.60) showed an inverse association. Our findings support the hypothesis that environmental pollutants interact with molecular hallmarks of aging.

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., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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 14-15years 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., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

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 polycyclic 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., (Copyright © 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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Polycyclic aromatic hydrocarbons (PAHs) are of interest to human biomonitoring studies due to their carcinogenic potential. Traditionally metabolites of these compounds, like 1-hydroxypyrene, are monitored in urine, but recent methods allow the determination of the parent compounds in urine, which give additional information regarding sources and toxicity of PAHs. In order to assess the feasibility of incorporating these methods in a human biomonitoring study, the 16 USEPA parent PAHs were determined in 20 urine samples. These samples were obtained from 10 boys and 10 girls aged 14-16 years, participating in the third Flemish Environment and Health Study (Flanders, Belgium). Of these 16 parent PAHs, nine could be determined in more than 95% of the samples and three (including benzo(a)pyrene) in more than 50%. Several correlations were found between different PAHs, but not between pyrene and its metabolite 1-hydroxypyrene. Diagnostic PAH ratios in urine and air samples pointed towards combustion sources and are in line with the ratios in environmental samples. Benzo(a)pyrene, naphthalene and fluorene have the highest carcinogenic potential in our cohort, when using toxic equivalency factors. Some associations between PAH congeners and determinants of exposure were found, while fluorene and acenaphthylene were positively associated with thyroid hormone levels and benzo(a)pyrene showed a positive correlation with DNA damage by comet assay. These results confirm that parent PAHs in urine are useful as biomarkers of exposure in biomonitoring studies., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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.

In this paper, based on the Flemish biomonitoring programs, we describe the associations between internal exposure to organochlorine pollutants and to cadmium (measured in 2004-2005 for adults aged 50-65 years) and self-reported health status obtained through a questionnaire in November 2011. Dioxin-like activity in serum showed a significant positive association with risk of cancer for women. After adjustment for confounders and covariates, the odds ratio for an exposure equal to the 90th percentile was 2.4 times higher than for an exposure equal to the 10th percentile. For both men and women dioxin-like activity and serum hexachlorobenzene (HCB) showed a significant positive association with risk of diabetes and of hypertension. Detailed analysis suggested that an increase in BMI might be part of the mechanism through which HCB contributes to diabetes and hypertension. Serum dichlorodiphenyldichloroethylene (p,p'-DDE) concentration showed a significant positive association with diabetes and hypertension in men, but not in women. Serum polychlorinated biphenyl (PCB) 118 showed a significant positive association with diabetes in both men and women, and after adjustment for correlated exposures, also with hypertension in men. Urinary cadmium concentrations showed a significant positive association with hypertension. Urinary cadmium concentrations were (in 2004-2005) significantly higher in persons who felt in less than good health (in 2011) than in persons who felt in very good health. After adjustment for correlated exposures (to HCB, p,p'-DDE and PCB118) marker PCBs showed a significant negative association with diabetes and hypertension. Serum p,p'-DDE showed in men a significant negative association with risk of diseases based on atheromata. Our findings suggest that exposure to pollutants can lead to an important increase in the risk of diseases such as cancer, diabetes and hypertension. Some pollutants may possibly also decrease the risk of some health problems, although this requires confirmation by other approaches., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

An excessive metal exposure is harmful to the brain. However, many aspects of metal neurotoxicity remain unclear including the magnitude of the low-level exposure effects and the level of exposure that can be assumed safe. The aim of our study was to investigate the association between a low-level metal exposure and three neurobehavioral domains (sustained attention, short-term memory, and manual motor speed). We measured Cd, Cu, Mn, Pb, and Tl in blood, Cd, Ni, and toxicologically relevant As in urine and methyl Hg in hair in 606 adolescents between 13.6 and 17 years of age. A two-fold increase in blood Cu was associated with a 0.37 standard deviations decrease in sustained attention (95% CI: -0.67 to -0.07, p=0.02) and 0.39 standard deviations decrease in short-term memory (95% CI: -0.70 to -0.07, p=0.02), accounting for gender, age, smoking, passive smoking, household income per capita, occupation of the parents, and education level of the mother. None of the other metals was significantly associated with the neurobehavioral domains that were measured. The observed associations between blood Cu and neurobehavioral performance are in line with recent studies in elderly. However, the relevance of our results for public health remains to be elucidated., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

The Flemish Centre for Environment and Health started with human biomonitoring in 2002 (FLEHS I: 2002-2006). The main goal of the second human biomonitoring cycle (FLEHS II: 2007-2011), was to determine mean values for a large number of pollutants in a representative sample of the general Flemish population. Values for Cd and Pb were updated, and a group of previously undetermined metals and metalloids (As, Mn, Cu and Tl) were included in some of the age groups. In this human biomonitoring program, three different age groups of the general Flemish population were monitored: 255 newborns and their mothers, 210 adolescents aged 14-15, and 204 adults between 20 and 40 years old. Trace elements were determined in cord blood and maternal blood of the mothers, in blood and urine of adolescents and in urine of adults. Determinants of life-style and personal factors were taken into account. The levels of trace elements in cord blood and maternal blood were for most elements at the lower end of the range found in literature. For Pb, As and Tl, a strong correlation (respectively r=0.43, 0.55 and 0.33; p<0.05) was found between levels in cord blood (respectively 8.6, 0.54 and 0.017 μg/L) and maternal blood (11.1, 0.64 and 0.028 μg/L), indicating that they are transported via the placenta from mother to fetus. The levels found in the adolescents and adults were compared with results from international biomonitoring studies, and were found to be in the same ranges. With the exception of Pb, all trace elements increased with increasing age group population. Finally, the results also showed that the levels of Cd and Pb in blood for this campaign (e.g. for Pb 8.6 and 14.8 μg/L in neonates and adolescents respectively) were lower compared to the first campaign (e.g. for Pb 14.7 and 21.7 μg/L in neonates and adolescents respectively), indicating a decrease over time. However, differences in sampling strategies might partially explain this observed trend., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

Background: In 2007, the second cycle of the Flemish human biomonitoring survey started, with a main focus on 14-15 year-old adolescents., Objectives: The main objectives were generating reference values for exposure markers, determining the pollution pressure in industrial hotspots and establishing dose-effect relationships between exposure to pollutants and hormone levels, sexual development, asthma and allergy, genotoxic and hematological markers., Methods: Geometric means with 95% confidence intervals (CI) were calculated for a reference population of 200 14-15 year-old adolescents. Stepwise multiple regression analyses with correction for confounders and covariates were performed to establish dose-effect relationships., Results: Geometric mean concentrations (with 95% CI) of 49.6 (45.7, 53.8), 70.8 (63.6, 78.8) and 8.34 (7.76, 8.97) n gg(-1) lipid for the sum of PCB 138, 153 and 180, p,p'-DDE and HCB were respectively 23%, 26% and 60% lower than those obtained five years earlier. Geometric mean concentrations of 108 (101, 114) and 32.1 (30.1, 34.2) pgCALUX-BEQg(-1) lipid were observed for the PCDD/Fs and dioxin-like PCBs, respectively. Multiple dose-effect relationships were observed between POPs and several effect markers, including positive (boys) and negative (girls) associations with data on sexual development and positive associations with asthma, animal allergy and free thyroxine (boys and girls)., Conclusions: Our findings suggest that chlorinated POP concentrations are decreasing over time and that even relatively low concentrations are associated with biological effects., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

In the Flemish human biomonitoring programme FLEHS II (2007-2011) trace metals (Cd, Pb, Cr, Ni, Cu, Mn, Tl, Sb, As and toxic relevant arsenic) were analysed in the blood and urine of adolescents (14-15 years old) in the reference population in Flanders and in areas of important industrial activities: Genk-Zuid and Menen. After adjustment of the results for confounding factors, the adolescents living in Genk-Zuid had higher levels of Cr, Cu and Tl in blood, higher levels of Cd and toxic relevant arsenic (TRA) in urine, but lower levels of Ni in blood and Sb in urine compared to the reference population. In Menen higher levels of Cd and Cu in urine, higher concentrations of Tl in blood but lower concentrations of Pb in blood and lower Ni, Sb and As in urine were found compared to the reference population. For both the reference population and the hot spots the concentrations are within the ranges found in other countries. Compared to the previous biomonitoring programme FLEHS I (2002-2006) a decrease in the concentrations of Cd and especially of Pb in blood was observed. However, it cannot be excluded that differences between the two campaigns are partially due to different sampling strategies., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

Animal studies showed that the developing brain is particularly sensitive to chemical exposure. Human studies carried out in areas with high exposures have proven neurodevelopmental disorders in relation to e.g. lead and PCBs. Whether these chemicals are associated with behavioural problems in childhood at current environmental levels is not well known. Therefore, we assessed the association between prenatal exposure to lead, cadmium, PCBs, dioxin-like compounds, HCB and p,p'-DDE and behavioural problems in 7-8year old children. Prenatal exposure data were obtained from the Flemish mother-new-born cohort. Lead, cadmium, PCBs, dioxin-like compounds, HCB and p,p'-DDE were analysed in cord blood. When the child reached 7-8years, 270 mothers completed the Strengths and Difficulties Questionnaire assessing their children's behavioural health. We found that doubling the prenatal lead exposure (cord blood lead levels) was associated with a 3.43 times higher risk for hyperactivity in both boys and girls. In addition, total difficulties were 5.08 times more likely in the highest tertile for prenatal lead exposure compared to the lowest tertile. In girls, total difficulties were 4.92 more likely when doubling cord blood p,p'-DDE, whereas no significant association was found in boys. Further, we noted in boys a 1.53 times higher risk for emotional problems when doubling cord blood cadmium, whereas no significant association was found in girls. These results indicate that the presence of environmental contaminants influences the mental health of the next generation., (© 2013.)

Background: Animal and in vitro studies demonstrated a neurotoxic potential of brominated flame retardants, a group of chemicals used in many household and commercial products to prevent fire. Although the first reports of detrimental neurobehavioral effects in rodents appeared more than ten years ago, human data are sparse., Methods: As a part of a biomonitoring program for environmental health surveillance in Flanders, Belgium, we assessed the neurobehavioral function with the Neurobehavioral Evaluation System (NES-3), and collected blood samples in a group of high school students. Cross-sectional data on 515 adolescents (13.6-17 years of age) was available for the analysis. Multiple regression models accounting for potential confounders were used to investigate the associations between biomarkers of internal exposure to brominated flame retardants [serum levels of polybrominated diphenyl ether (PBDE) congeners 47, 99, 100, 153, 209, hexabromocyclododecane (HBCD), and tetrabromobisphenol A (TBBPA)] and cognitive performance. In addition, we investigated the association between brominated flame retardants and serum levels of FT3, FT4, and TSH., Results: A two-fold increase of the sum of serum PBDE's was associated with a decrease of the number of taps with the preferred-hand in the Finger Tapping test by 5.31 (95% CI: 0.56 to 10.05, p = 0.029). The effects of the individual PBDE congeners on the motor speed were consistent. Serum levels above the level of quantification were associated with an average decrease of FT3 level by 0.18 pg/mL (95% CI: 0.03 to 0.34, p = 0.020) for PBDE-99 and by 0.15 pg/mL (95% CI: 0.004 to 0.29, p = 0.045) for PBDE-100, compared with concentrations below the level of quantification. PBDE-47 level above the level of quantification was associated with an average increase of TSH levels by 10.1% (95% CI: 0.8% to 20.2%, p = 0.033), compared with concentrations below the level of quantification. We did not observe effects of PBDE's on neurobehavioral domains other than the motor function. HBCD and TBBPA did not show consistent associations with performance in the neurobehavioral tests., Conclusions: This study is one of few studies and so far the largest one investigating the neurobehavioral effects of brominated flame retardants in humans. Consistently with experimental animal data, PBDE exposure was associated with changes in the motor function and the serum levels of the thyroid hormones.

Background: Environmental justice research suggests that inequalities in the distribution of environmental exposure to chemical pollution systematically disadvantage the lower social strata of society. The effects of these inequalities on the human exposure to pollution are however to a large extend unknown. The purpose of this study is to assess social gradients in human biomonitoring results of a representative sample of Flemish adolescents., Methods: We investigate the associations between individual socioeconomic status (SES), measured by parental educational attainments, and internal body concentration of seven chemical compounds in biological samples of 1642 adolescents aged 14-15 in Flanders (Belgium): PCBs, HCB, DDE, lead, cadmium, benzene and PAHs. Social gradients in average and high exposure to these biomarkers were examined with geometric means and odds ratios (with 95% confidence intervals), using multiple regression models, controlling for covariates and confounders., Results: Depending on the (type of) pollutant, adolescents with a lower SES either have higher or lower internal concentrations. Chlorinated compounds (PCBs and pesticides HCB and DDE) are positively associated with SES (higher exposures for higher SES), while heavy metals (lead and cadmium) are negatively associated (higher exposures for lower SES). For metabolites of organic compounds (benzene and PAHs) we find no association with SES. Socially constructed factors, such as dietary and lifestyle habits, play an important role in these relations., Conclusions: Our study suggests that the association between individual SES and the internal body concentration of exposure to environmental pollutants in Flemish adolescents is more complex than can be assumed on the basis of the environmental justice hypothesis., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

Flanders is densely populated with much industry and intensive farming. Sexual maturation of adolescents (aged 14-15 years) was studied in relation to internal exposure to pollutants. Serum levels of pollutants and sex hormones were measured in 1679 participants selected as a random sample of the adolescents residing in the study areas. Data on sexual development were obtained from the medical school examination files. Self-assessment questionnaires provided information on health, use of medication and lifestyle factors. In boys, serum levels of hexachlorobenzene (HCB), p,p'-DDE and polychlorinated biphenyls (sum of marker PCB138, 153 and 180) were significantly and positively associated with pubertal staging (pubic hair and genital development). Higher levels of serum HCB and blood lead were associated with, respectively, a lower and a higher risk of gynecomastia. In girls, significant and negative associations were detected between blood lead and pubic hair development; higher exposure to PCBs was significantly associated with a delay in timing of menarche. Environmental exposures to pollutants at levels actually present in the Flemish population are associated with measurable effects on pubertal development. However, further understanding of toxic mode of action and sensitive windows of exposure is needed to explain the current findings.

Flanders is densely populated with much industry and intensive farming. Hormonal status of 14- to 15-year-old male adolescents was studied in relation to internal exposure to pollutants. A total of 887 participants were selected as a random sample of the adolescents residing in the study areas. Confounding factors and significant covariates were taken into account. Serum levels of testosterone, free testosterone and estradiol, and the aromatase index showed significant positive associations with serum levels of marker polychlorobiphenyls (sum of PCBs 138, 153, and 180) and of hexachlorobenzene (HCB) and a negative association with urinary cadmium concentration. Serum levels of estradiol also showed a positive association with serum levels of dichlorodiphenyldichloroethylene (DDE). A doubling of serum concentrations of marker PCBs and HCB and of urinary concentration of cadmium were, respectively, associated with an increase of 16.4% (P<0.00001) and 16.6% (P<0.001) and a decrease of 9.6% (P<0.001) in serum testosterone concentration. Similar findings were made after additional adjustment for concurrent exposures. Associations between biological effects and internal exposures were, in terms of the regression coefficient, often stronger at exposures below the median. Environmental exposures to pollutants resulting in "normal" levels of internal exposure were associated with quite substantial differences in hormone concentrations.

Flanders is densely populated with much industry and intensive farming. Body size of 14- to 15-year old adolescents and of adults aged 50-65 was studied in relation to internal exposure to pollutants. 1679 adolescents (887 boys and 792 girls), 775 men and 808 women were selected as a random sample of the population. Concentrations of pollutants in blood or urine were measured in accordance with quality control/quality assurance procedures. Self-assessment questionnaires provided information on personal and life-style factors. Height and weight of subjects were measured. Confounding factors and significant covariates were taken into account. For boys and girls, height and body mass index (BMI) showed a negative association with urinary concentration of cadmium and BMI also with serum concentration of hexachlorobenzene (HCB) and with the sum of serum concentrations of polychlorinated biphenyls (PCBs) 138, 153, and 180 (marker PCBs), whereas BMI showed a positive association with serum concentration of PCB 118. For boys, height showed a negative association with urinary concentration of 1-hydroxypyrene (1-OHP) and positive associations with serum concentrations of HCB and PCB 118. For adults no significant associations between internal exposure and height were observed. For men, BMI showed negative associations with urinary cadmium concentration and with serum levels of marker PCBs and positive associations with serum levels of HCB, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), PCB 118 and the dioxin fraction of dioxin-like activity. For women, BMI showed a negative association with urinary cadmium concentration, with blood lead concentration and with the concentration of marker PCBs in serum, and a positive association with serum concentrations of HCB, p,p'-DDE and PCB 118. Associations between biological effects and internal exposures were, in terms of the regression coefficient, often stronger at exposures below the median. Environmental exposures to pollutants resulting in "normal" levels of internal exposure were associated with quite substantial differences in body mass index.

To collect regional information on internal levels of pollutants in humans in Flanders, 1196 mother-child pairs were systematically recruited in 2002-2003 via 25 maternities across Flanders. Cd, Pb, PCB congeners 118, 170, 138, 153 and 180, p,p'-DDE - a key metabolite of DDT- and hexachlorobenzene (HCB) were measured in cord blood or plasma. Cd was detected in 64% of the samples (geometric mean 0.21 microg/L cord blood). p,p'-DDE (110 ng/g plasma lipids) and Pb (14.7 microg/L blood), were measurable in nearly all samples. The individual PCB congeners could be detected in 40 to 81% of the newborns (138+153+180=64.4 ng/g plasma lipids). HCB (18.9 ng/g plasma lipids) and dioxin-like compounds measured by DR-CALUX(R) (23 pg CALUX-TEQ/g lipids) were above detection limit in more than 75% of the samples. Age and smoking habits of the mothers, did not influence the cord blood Pb and Cd levels. The organochlorines increased 4 to 9% per year of the mother's age (partial R(2)=0.05 to 0.22). Mothers had 2.6% less PCBs in cord blood (partial R(2)=0.02) for each unit increase in pre-pregnancy BMI. Season of delivery, breastfeeding previous children or consumption of local dairy products, were minor determinants. Up to 20% of the variability in organochlorine concentrations was explained by residence area. It was concluded that the place of birth in Flanders is an important determinant of the load of pollutants measured at the start of life. This underlines the validity of human biomonitoring on (relatively) small geographical scale.

Objective: We investigated the association between body mass index (BMI) standard deviation score (SDS) and prenatal exposure to hexachlorobenzene, dichlorodiphenyldichloroethylene (DDE), dioxin-like compounds, and polychlorinated biphenyls (PCBs)., Methods: In this prospective birth cohort study, we assessed a random sample of mother-infant pairs (n = 138) living in Flanders, Belgium, with follow-up until the children were 3 years of age. We measured body mass index as standard deviation scores (BMI SDS) of children 1-3 years of age as well as pollutants measured in cord blood., Results: DDE correlated with BMI SDS, with effect modification by maternal smoking and the child's age. At 1 year, children of smoking mothers had higher BMI SDS than did children of nonsmoking mothers. At 3 years, this difference was reduced because of the faster rate of decline in BMI SDS in the former group. This relationship held except for children with high levels of DDE. DDE had a small effect on BMI SDS at 3 years of age in children of nonsmoking mothers (difference in BMI SDS for DDE concentrations between the 90th and 10th percentiles = 0.13). On the other hand, smoking enhanced the relation between DDE and BMI SDS at 3 years (difference in BMI SDS for DDE concentrations between the 90th and 10th percentiles = 0.76). Increasing concentrations of PCBs were associated with higher BMI SDS values at all ages (parameter estimate = 0.003 +/- 0.001; p = 0.03)., Conclusion: In this study we demonstrated that intrauterine exposure to DDE and PCBs is associated with BMI during early childhood. Future studies are warranted to confirm our findings and to assess possible mechanisms by which these pollutants could alter energy metabolism.

Persistent organic pollutants (POPs) are chemicals that accumulate in the food chain and are toxic to humans and wildlife. The fourth World Health Organization (WHO) survey on POP levels in human milk (2006-2009) aims to provide baseline and trend information on human exposure to POPs. So far Belgium participated in all three previous rounds (1988, 1992, 2001). Whereas the first three rounds focused on determination of dioxins and PCBs in pooled (mixed) samples, the fourth survey comprised the analyses of individual milk samples for nine "basic POPs" (chlorinated pesticides and indicator PCBs) and of pooled milk samples for "basic POPs", "advanced POPs" (dioxins and dioxin-like PCBs) and "optional POPs" (polybrominated diphenylethers [PBDEs], polybrominated dioxins and dibenzofurans [PBrDD/F], mixed halogenated dioxins and dibenzofurans [PXDD/F] and hexabromocyclododecane [HBCD]). For the Belgian participation human milk samples were collected during the summer of 2006 from 197 women between 18 and 30 years old distributed over all Belgian provinces. The individual samples were analyzed in a Belgian Laboratory for "basic" POPs. A pooled sample was made from 178 individual samples and analyzed by the WHO Reference Laboratory for the "basic, advanced and optional" POPs. The results indicate that most organochlorinated pesticides banned 25-30 years ago were below or around detection limits in Belgian human milk samples although DDE was still found at low levels in all samples. Over the last five years the levels of marker PCBs and PCDD/Fs in Belgian human milk decreased, respectively, by 58% and 39%. For some of the other emerging or older compounds recent international data are needed to allow comparison. This shows the importance of international studies as run by WHO.

Background: This study intended to investigate whether residence in areas polluted by heavy industry, waste incineration, a high density of traffic and housing or intensive use of pesticides, could contribute to the high incidence of cancer observed in Flanders., Methods: Subjects were 1583 residents aged 50-65 from 9 areas with different types of pollution. Cadmium, lead, p,p'-DDE, hexachlorobenzene, PCBs and dioxin-like activity (Calux test) were measured in blood, and cadmium, t,t'-muconic acid and 1-hydroxypyrene in urine. Effect biomarkers were prostate specific antigen, carcinoembryonic antigen and p53 protein serum levels, number of micronuclei per 1000 binucleated peripheral blood cells, DNA damage (comet assay) in peripheral blood cells and 8-hydroxy-deoxyguanosine in urine. Confounding factors were taken into account., Results: Overall significant differences between areas were found for carcinoembryonic antigen, micronuclei, 8-hydroxy-deoxyguanosine and DNA damage. Compared to a rural area with mainly fruit production, effect biomarkers were often significantly elevated around waste incinerators, in the cities of Antwerp and Ghent, in industrial areas and also in other rural areas. Within an industrial area DNA strand break levels were almost three times higher close to industrial installations than 5 kilometres upwind of the main industrial installations (p < 0.0001). Positive exposure-effect relationships were found for carcinoembryonic antigen (urinary cadmium, t,t'-muconic acid, 1-hydroxypyrene and blood lead), micronuclei (PCB118), DNA damage (PCB118) and 8-hydroxy-deoxyguanosine (t,t'-muconic acid, 1-hydroxypyrene). Also, we found significant associations between values of PSA above the p90 and higher values of urinary cadmium, between values of p53 above the p90 and higher serum levels of p,p'-DDE, hexachlorobenzene and marker PCBs (PCB 138, 153 and 180) and between serum levels of p,p'-DDE above the p90 and higher serum values of carcinoembryonic antigen. Significant associations were also found between effect biomarkers and occupational or lifestyle parameters., Conclusion: Levels of internal exposure, and residence near waste incinerators, in cities, or close to important industries, but not in areas with intensive use of pesticides, showed positive correlations with biomarkers associated with carcinogenesis and thus probably contribute to risk of cancer. In some rural areas, the levels of these biomarkers were not lower than in the rest of Flanders.

Background: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and some related environmental contaminants are aryl hydrocarbon receptor (AhR) ligands that exert reproductive and developmental toxicity in laboratory animals. In humans, fertility-related effects are less documented., Objective: The aim of this study was to investigate the relationship between dioxin-like biological activity in serum and parameters of reproductive status in men from the general population 5 months after a polychlorinated biphenyl and dioxin food-contamination episode in Belgium., Design: In the framework of the cross-sectional Flemish Environment and Health Study (FLEHS), we recruited 101 men 20-40 years of age and evaluated sperm parameters, measured sex hormones, and gathered information on a number of lifestyle factors. In addition, we determined the AhR-mediated enzymatic response elicited by individual serum samples and expressed it as TCDD equivalent concentrations (CALUX-TEQs) using an established transactivation assay., Results: Age (p = 0.04) and the frequency of fish (p = 0.02) and egg (p = 0.001) consumption were independent positive determinants of serum dioxin-like activity. After correcting for possible confounders, we found that a 2-fold increase in CALUX-TEQ > 16 pg/L was associated with a 7.1% and 6.8% (both p = 0.04) decrease in total and free testosterone, respectively. We also observed a more pronounced drop in semen volume of 16.0% (p = 0.03), whereas sperm concentration rose by 25.2% (p = 0.07). No relationship was found with total sperm count or sperm morphology., Conclusions: These data suggest an interaction of dioxin-like compounds with the secretory function of the seminal vesicles or prostate, possibly indirectly through an effect on testosterone secretion, at levels not affecting spermatogenesis as such.

We measured tumor-associated proteins (TAPs) and pollutants in blood, serum, and urine of 200 nonsmoking women 50-65 years of age, residing in the rural municipality of Peer or in Hoboken or Wilrijk, industrial suburbs of Antwerp, Belgium. Persons with occupational exposures or commuting to other towns were excluded. Residents from Hoboken had significantly higher levels of blood lead and serum zinc and polychlorinated biphenyls. Surprisingly, residents of Peer had significantly higher levels of serum cadmium, dioxin-like activity in blood fat, and urinary 1-hydroxypyrene. For 5 of the 12 TAPs assessed in this study, we observed significant differences in serum levels among residents of the three municipalities after adjusting for personal or lifestyle parameters. Although we found levels of internal exposure to pollutants to be quite homogeneous in Flanders, we found significantly higher levels of TAPs only in the industrial suburbs. In multiple regression with all 29 available personal, lifestyle, and internal exposure parameters, blood lead levels showed a positive association with serum levels of anti-p53, carcino-embryonic antigen (CEA), and tissue polypeptide-specific antigen (TPS) and with an index for mean TAP level (I(tap)); dioxin-like activity in serum and serum copper showed a positive association with serum CA 125 (cancer antigen 125); and serum zinc showed a positive association with serum levels of c-erbB-2 ectodomain and TPS. An index of internal exposure showed a positive association with serum levels of both CEA and anti-p53 and with I(tap). This study provides some evidence that levels of internal exposure such as those present in Flanders, in particular concerning lead, are indeed associated with biologic effects.

In 1999, the FLEHS was set by the Flemish Ministry of Health, Belgium to assess pollutant concentrations and related health effect biomarkers in humans living in Flanders. Concentrations of selected organochlorine pesticides, polychlorinated biphenyls (PCB) and polychlorinated dibenzo-p-dioxins (PCDD) and furans (PCDF) were measured by gas chromatography-mass spectrometry and Chemical-Activated LUciferase gene eXpression (CALUX) bioassay in 47 serum pools of 200 women between 50 and 65 years living in two areas of Flanders. Correlation between TEQ values of different groups of compounds were computed in these pool results and it was found that total toxic equivalencies (TEQs) correlated well with the values of the groups of contributing compounds: mono-ortho PCBs (r = 0.77), non-ortho PCBs (r = 0.65) and PCDD/Fs (r = 0.88). The total TEQ was lower correlated to the CALUX-TEQ (r = 0.57). When calculating associations between those classes of compounds in the two studied regions separately, they were all higher correlated in the urban area compared to the more rural region. High correlation coefficients (r > 0.80) were also calculated between individual compounds and groups of compounds. It was suggested that in this studied background-exposed population, some compounds could be good predictors for a group: e.g. PCB 153 for indicator and total PCBs, PCB 118 for total PCB TEQ, PCB 156 for mono-ortho PCB-TEQs and total TEQ, 2,3,4,7,8-P5CDF for PCDD/F TEQs and total TEQs. This means that in pooled serum samples correlations between persistent organochlorine compounds are as strong as for individual POP measurements observed in earlier studies.