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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.)

Introduction: Pesticides, including herbicides, are widely used for agricultural and sanitary reasons and concerns have been raised about their various health effects. Little research has been done into the extent to which agricultural land use in the residential surroundings contributes to (internal) exposure of pesticides., Objectives: We investigated the associations between the proportion of agricultural land use around the residence and the exposure to pesticides in adolescents in Flanders (Belgium)., Material and Methods: We included 424 adolescents participating in the fourth Flemish Environment and Health Study (FLEHS IV) between 2016 and 2020. The residential address of all participants was geocoded and the proportion of agricultural land use around the residence was estimated in several buffers (300 m, 500 m, 1000 m and 2000 m). The concentrations of the following biomarkers of pesticides were measured in urine and adjusted for the specific gravity: glyphosate and its metabolite, aminomethyl-phosphonic acid (AMPA); 3-phenoxybenzoic acid (3-PBA); 3,5,6-trichloro-2-pyridinol (TCPy) and 2,4-dichlophenoxy-acetic acid (2,4-D). We categorized the pesticide biomarkers in three categories according to the exposure levels and used ordinal logistic regression models adjusted for sex, season and household education to estimate the odds ratio for an increase in an interquartile range (IQR) of proportion of agricultural land use. We also used binary logistic regression models in which the category of highest exposure was compared to the category of lowest exposure. In addition, we explored potential effect modification by sex and season., Results: We found a significant association between the proportion of agricultural land use in a buffer of 2000 m around the residence and the levels of urinary AMPA divided into three categories (OR = 1.35 for an IQR increase in the proportion of agricultural land use around residence; 95% CI: 1.00-1.83). This association was less pronounced and not statistically significant for the other studied pesticides (OR ranging between 0.95 and 1.16). Stratified analysis showed the strongest association of the proportion of agricultural land use within 2000 m buffers for AMPA among boys (OR = 1.89; 95% CI: 1.19-3.04). Results using smaller buffers were comparable, but did not reach statistical significance., Conclusion: Our findings suggest that a higher proportion of agricultural land use around the residence might increase exposure to AMPA., Competing Interests: Declaration of competing interest All authors declare they have no competing interest., (Copyright © 2022. Published by Elsevier GmbH.)

Background/aim: Glyphosate, a broad-spectrum herbicide, and its main metabolite aminomethylphosphonic acid (AMPA) are persistent in the environment. Studies showed associations between glyphosate or AMPA exposure and several adverse cellular processes, including metabolic alterations and oxidative stress., Objective: To determine the association between glyphosate and AMPA exposure and biomarkers of biological aging., Methods: We examined glyphosate and AMPA exposure, mtDNA content and leukocyte telomere length in 181 adults, included in the third cycle of the Flemish Environment and Health Study (FLEHSIII). DNA was isolated from leukocytes and the relative mtDNA content and telomere length were determined using qPCR. Urinary glyphosate and AMPA concentrations were measured by Gas Chromatography-Tandem Mass Spectrometry (GC-MS-MS). We used multiple linear regression models to associate mtDNA content and leukocyte telomere length with glyphosate or AMPA exposure while adjusting for confounding variables., Results: A doubling in urinary AMPA concentration was associated with 5.19% (95% CI: 0.49 to 10.11; p = 0.03) longer leukocyte telomere length, while no association was observed with urinary glyphosate concentration. No association between mtDNA content and urinary glyphosate nor AMPA levels was observed., Conclusions: This study showed that AMPA exposure may be associated with telomere biology in adults., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

To improve our understanding of internal exposure to multiple chemicals, the concept exposure load (EL) was used on human biomonitoring (HBM) data of the 4th FLEHS (Flemish Environment and Health Study; 2016-2020). The investigated chemicals were per- and polyfluoroalkyl substances (PFASs), bisphenols, phthalates and alternative plasticizers, flame retardants, pesticides, toxic metals, organochlorine compounds and polycyclic aromatic hydrocarbons (PAHs). The EL calculates "the number of chemicals to which individuals are internally exposed above a predefined threshold". In this study, the 50th and 90th percentile of each of the 45 chemicals were applied as thresholds for the EL calculations for 387 study participants. Around 20% of the participants were exposed to >27 chemicals above the P50 and to >6 chemicals above the P90 level. This shows that participants can be internally exposed to multiple chemicals in relatively high concentrations. When the chemical composition of the EL was considered, the variability between individuals was driven by some chemicals more than others. The variability of the chemical profiles at high exposure loads (EL-P90) was somewhat dominated by e.g. organochlorine chemicals, PFASs, phthalates, PAHs, organophosphate flame retardants, bisphenols (A & F), pesticides, metals, but to a lesser extent by brominated flame retardants, the organophosphorus flame retardants TCIPP & TBOEP, naphthalene and benzene, bisphenols S, B & Z, the pesticide 2,4-D, the phthalate DEP and alternative plasticizer DINCH. Associations between the EL and exposure determinants suggested determinants formerly associated with fat soluble chemicals, PFASs, bisphenols, and PAHs. This information adds to the knowledge needed to reduce the exposure by policymakers and citizens. However, a more in depth study is necessary to explore in detail the causes for the higher EL in some individuals. Some limitations in the EL concept are that a binary number is used for exposure above or below a threshold, while toxicity and residence time in the body are not accounted for and the sequence of exposure in different life stages is unknown. However, EL is a first useful step to get more insight in multiple chemical exposure in higher exposed subpopulations (relative to the rest of the sampled population)., (Copyright © 2021. Published by Elsevier GmbH.)

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.)

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.)

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.)

Due to possible health risks, quantification of mercury accumulation in humans was included in the Flemish biomonitoring programmes FLEHS I (2002-2006) and FLEHS II (2007-2011). The general objective of FLEHS I was to assess regional exposure levels in order to link possible differences in these internal exposure levels to different types of local environmental pressure. Therefore, Hg and MMHg (methylmercury) were only measured in pooled blood samples per region and per age class. In FLEHS II, mercury concentrations were measured in hair of each participant. About 200 adolescents and 250 mothers (reference group) and two times 200 adolescents (2 hotspots) were screened. The main objectives of the FLEHS II study were: (1) to determine reference levels of mercury in hair for Flanders; (2) to assess relations between mercury exposure and possible sources like fish consumption; (3) to assess dose-effect relations between mercury exposure and health effect markers. The results showed that mercury concentrations in the Flemish population were rather low compared to other studies. Mercury levels in the Flemish populations were strongly related to the age of the participants and consumption of fish. Significant negative associations were observed between mercury in hair and asthma, having received breast feeding as a newborn, age at menarche in girls, allergy for animals and free testosterone levels. Significant correlations were also observed between mercury in hair and genes JAK2, ARID4A, Hist1HA4L (boys) and HLAdrb5, PIAS2, MANN1B1, GIT and ABCA1 (girls)., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

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.)

Since 2002 a human biomonitoring network has been established in Flanders (Belgium) as part of a programme on environmental health surveillance. The human biomonitoring network should support environmental health policy by identifying priorities for further action. The first cycle of the programme (2002-2006) confirmed the hypotheses that living in areas with different environmental pressure is reflected in different loads of environmental chemicals in the residents. In the second cycle of the programme (2007-2011) the number of environmental chemicals for which human biomonitoring data were obtained was expanded substantially. The goal of the Flemish programme is to use and translate the scientific results into policy actions. Its further orientation in the second cycle to human biomonitoring in hot spots and sensitive age groups or susceptible persons with underlying complications (e.g. persons with diabetes) are linked to these goals. Interaction with stakeholders is embedded in the programme emphasizing transparency of the choices that are made and direct communication. The Flemish human biomonitoring programme is organized centrally with major involvement of research partners from different disciplines which allows engrafting environmental health research on the programme. One of the major focuses is the question whether combinations of pollutants in the general population are associated with biological effects. The objective of this paper is to review and discuss the options that were taken in the human biomonitoring programme in order to achieve its goals., (Copyright © 2011 Elsevier GmbH. All rights reserved.)