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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 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.)

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.)

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.

The production of CO2 and formate in isolated rat hepatocytes incubated in the presence of 3-methyl[1-14C]margaric acid was investigated. Production rates of formate were approximately 4-fold lower than those of CO2. Aminotriazole (3-amino-1, 2, 4-triazole), an irreversible inhibitor of catalase, potently suppressed alpha-oxidation of 3-methylmargaric acid, whereas beta-oxidation of palmitate, 2-methylpalmitate and trihydroxycoprostanic acid and conversion of exogenously added formate to CO2 were not or only slightly affected. This shows that aminotriazole is not only an inhibitor of catalase, but also of alpha-oxidation of 3-methyl-substituted fatty acids.