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Background: Asthma and allergic diseases are among the common causes of morbidity and mortality globally. Various environmental pollutants are linked to the development of asthma and allergic diseases. Evidence on the role of oxidative stress and immune markers in the association of environmental pollutants with asthma and allergy is scant. We examined cross-sectional associations between environmental pollutants and asthma and allergy, investigated mixture effects and possible mediation by oxidative stress or immune markers., Methods: We used data from the Flemish Environment and Health Study 2016-2020 (FLEHS IV), including 409 adolescents aged 13-16 years. Fifty-four pollutants, including metals, phthalates, Di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH), bisphenols, currently used and legacy pesticides, flame retardants, per- and polyfluoroalkyl substances (PFAS), polyaromatic hydrocarbons (PAHs), and polychlorinated biphenyls (PCBs) were analyzed. Outcomes were self-reported asthma, rhinitis, eczema, allergies, respiratory infection, and airway inflammation, measured through fractional exhaled nitric oxide (FeNO). Single pollutant models using multiple regression analysis and multipollutant models using Bayesian Kernel Machine Regression (BKMR) were fitted. As sensitivity analysis, Bayesian model averaging (BMA) and elastic net (ENET) models were also performed. For Bayesian models, posterior inclusion probabilities (PIP) were used to identify the most important chemicals. Mediation analysis was performed to investigate the role of oxidative stress, measured by urinary 8-hydroxy-2' -deoxyguanosine (8-OHdG), and immune markers (eosinophils, basophils, InterLeukin 8, InterLeukin 6, and Interferon-ᵧ in blood)., Results: In single pollutant models, FeNO was significantly higher by 20% (95% CI: 6, 36%) and 13% (95% CI: 2, 25%) per interquartile range (IQR) fold in mono-n-butyl phthalate (MnBP) and mono-benzyl phthalate (MBzP), respectively. In BKMR analysis, the group PIPs indicated phthalates and DINCH as the most important group (group PIP = 0.509), with MnBP being the most important pollutant within that group (conditional PIP = 0.564; %change = 28%; 95%CI: 6, 54%). Similar patterns were observed in all multipollutant models. Eosinophil count mediated 37.8% (p = 0.018) and 27.9% (p = 0.045) of the association between MBzP and FeNO, and the association between MnBP and FeNO, respectively. 8-OHdG plays a significant mediating role in the association of 2,4-Dichlorophenoxyacetic acid (2,4-D) (55.4%), 3,5,6-Trichloro-2-pyridinol (TCPY) (48.1%), and 1-Naphthylamine (1-NAP) (32.7%) with rhinitis, while the total effects of these chemicals on rhinitis were not statistically significant., Conclusions: This study found associations between phthalates, MnBP and MBzP, and elevated FeNO, which appeared to be mediated by eosinophil count. 8-OHdG plays a significant mediating role in the association between 2,4-D, TCPY, and 1-NAP with rhinitis, while their direct effects remain non-significant. Use of inflammatory and oxidative stress markers can enhance the understanding of inflammatory processes in asthma and allergic diseases due to environmental pollutants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Exposure to air pollution and traffic noise are associated with adverse health outcomes in adolescents. Chronic endocrine stress and systemic inflammation have been hypothesized to underlie the adverse health effects. Simultaneous assessment of inflammation and chronic endocrine stress in epidemiological studies is lacking. The aim of the study was to investigate biomarkers of chronic endocrine stress and inflammation in relation to long-term residential exposure to air pollution and traffic noise in adolescents., Methods: In Flemish adolescents (14-15 years), we determined hair cortisol concentration (HCC) as a chronic stress biomarker in 3-cm scalp-near hair sections (n = 395), and leucocyte and leucocyte subtype counts (neutrophils, monocytes, lymphocytes) as inflammatory biomarkers in peripheral blood (n = 385). Daily particulate matter (PM 2.5 , PM 10 ), nitrogen dioxide (NO 2 ) and black carbon (BC) concentrations were modelled at the residential address and averaged over 3-month and 1-year periods prior to sampling. Residential traffic noise level was estimated and classified in 5 dB intervals. Sex-specific associations between residential exposures and effect biomarkers were studied using linear regression models, adjusted for a priori selected covariates., Results: In boys, HCC increased with a factor 1.30 (95% CI: 1.10, 1.54) for an increase in 1-year mean NO 2 from the 25th to 75th percentile (p75/p25), after adjustment for age, BMI, personal and neighborhood socioeconomic status. The corresponding estimate for PM 10 was 1.24 (95% CI: 1.02, 1.51). Total leucocyte count in boys, adjusted for the aforementioned covariates and recent health complaints, was positively associated with PM 2.5, PM 10 , NO 2 and BC. In particular, the neutrophil count increased with a factor 1.11 (95% CI: 1.03, 1.19) for a (p75/p25)-factor increase in 1-year mean BC, corresponding estimates for PM 2.5, PM 10 and NO 2 were 1.10 (95% CI: 1.01, 1.19), 1.10 (95% CI: 1.01, 1.20) and 1.08 (95% CI: 1.00, 1.16). Lymphocyte count increased with a factor 1.05 (95% CI: 1.01, 1.10) for a (p75/p25)-factor increase in 1-year mean NO 2 . Similar results were observed for 3-month mean exposures. Results were robust to adjustment for recent air pollution exposure. In girls, air pollutants were not associated with HCC or differential leucocyte count. Residential traffic noise level was not associated with HCC or leucocyte counts in boys nor girls., Conclusions: Long-term residential exposure to air pollutants was positively associated with chronic endocrine stress and inflammation in adolescent boys, not in girls. This study may contribute to a better understanding of the early pathophysiological changes that may underlie adverse health effects of air pollution exposure in adolescents., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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.)

Introduction: Traffic-related air pollution has been shown to induce neurotoxicity in rodents. Several recent epidemiological studies reported negative associations between residential outdoor air pollution and neurobehavioral performance. We investigated in a population of non-smoker adolescents the associations between the urinary concentration of trans, trans-muconic acid (t,t-MA-U), a metabolite of benzene and used as proxy-biomarker of traffic exposure, and two neurobehavioral domains, i.e. sustained attention and short-term memory., Methods: In the framework of an environmental health surveillance study in Flanders (Belgium), we examined between 2008 and 2014 grade nine high school students (n=895). We used reaction time, number of omission errors, and number of commission errors in the Continuous Performance Test to evaluate sustained attention, and for the evaluation of short-term memory we used maximum digit span forward and backward of the Digit Span Test. We measured blood lead (PbB) to assess the independent effect of t,t-MA-U on neurobehavioral outcomes., Results: This neurobehavioral examination study showed that a ten-fold increase in t,t-MA-U was associated with a 0.14 SD lower sustained attention (95% Confidence Interval: -0.26 to -0.019; p=0.02) and a 0.17 SD diminished short-term memory (95% CI: -0.31 to -0.030; p=0.02). For the same increment in t,t-MA-U, the Continuous Performance Test showed a 12.2ms higher mean reaction time (95% CI: 4.86-19.5; p=0.001) and 0.51 more numbers of errors of omission (95% CI: 0.057-0.97; p=0.028), while no significant association was found with errors of commission. For the Digit Span Tests, the maximum digit span forward was associated with a 0.20 lower number of digits (95% CI: -0.38 to -0.026; p=0.025) and maximum digit span backward with -0.15 digits (95% CI: -0.32 to 0.022; p=0.088). These associations were independent of PbB, parental education and other important covariates including gender, age, passive smoking, ethnicity, urinary creatinine, time of the day, and examination day of the week. For PbB, an independent association was only found with mean reaction time of the Continuous Performance Test (19.1ms, 95% CI: 2.43-35.8; p=0.025)., Conclusions: In adolescents, a ten-fold increase in the concentration of t,t-MA-U, used as a proxy-biomarker for traffic-related exposure, was associated with a significant deficit in sustained attention and short-term memory. The public health implications of this finding cannot be overlooked as the effect-size for these neurobehavioral domains was about 40% of the effect-size of parental education., (Copyright © 2016. Published by Elsevier Inc.)

As part of the second Flemish Environment and Health Study (FLEHS II), bisphenol-A (BPA) and different phthalate metabolites were analyzed, for the first time, in the urine of 210 adolescents in Flanders, Belgium. All chemicals had a detection frequency above 90%. For all compounds, except the sum of DEHP, highest levels were detected during spring. Average values for the Flemish adolescents were in an agreement with concentrations found in different international studies, all confirming the ubiquity of BPA and phthalate exposure. There was a significant correlation between BPA and the different phthalate metabolites (r between 0.26 and 0.39; p<0.01). Shared sources of exposure to BPA and phthalates, such as food packaging, were suggested to be responsible for this positive correlation. Different determinants of exposure were evaluated in relation to the urinary concentrations of these chemicals. For BPA, a significant association was observed with household income class, smoking and exposure to environmental tobacco smoke. For phthalates, the following significant associations were observed: age (MBzP), educational level of the adolescent (MBzP), equivalent household income (MnBP), use of personal care products (MnBP and MBzP), wall paper in house (MnBP and MBzP) and use of local vegetables (MnBP and MBzP)., (Copyright © 2014 Elsevier Inc. All rights reserved.)

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 R2, 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 by age. For biomarkers of persistent pollutants that reflect long-term exposure, the relation between the covariates and the biomarkers can be well quantified.