Network Analysis to Identify Communities Among Multiple Exposure Biomarkers Measured at Birth in Three Flemish General Population Samples.

Introduction: Humans are exposed to multiple environmental chemicals via different sources resulting in complex real-life exposure patterns. Insight into these patterns is important for applications such as linkage to health effects and (mixture) risk assessment. By providing internal exposure levels of (metabolites of) chemicals, biomonitoring studies can provide snapshots of exposure patterns and factors that drive them. Presentation of biomonitoring data in networks facilitates the detection of such exposure patterns and allows for the systematic comparison of observed exposure patterns between datasets and strata within datasets. Methods: We demonstrate the use of network techniques in human biomonitoring data from cord blood samples collected in three campaigns of the Flemish Environment and Health Studies (FLEHS) (sampling years resp. 2002-2004, 2008-2009, and 2013-2014). Measured biomarkers were multiple organochlorine compounds, PFAS and metals. Comparative network analysis (CNA) was conducted to systematically compare networks between sampling campaigns, smoking status during pregnancy, and maternal pre-pregnancy BMI. Results: Network techniques offered an intuitive approach to visualize complex correlation structures within human biomonitoring data. The identification of groups of highly connected biomarkers, "communities," within these networks highlighted which biomarkers should be considered collectively in the analysis and interpretation of epidemiological studies or in the design of toxicological mixture studies. Network analyses demonstrated in our example to which extent biomarker networks and its communities changed across the sampling campaigns, smoking status during pregnancy, and maternal pre-pregnancy BMI. Conclusion: Network analysis is a data-driven and intuitive screening method when dealing with multiple exposure biomarkers, which can easily be upscaled to high dimensional HBM datasets, and can inform mixture risk assessment approaches.

Three cycles of human biomonitoring in Flanders - Time trends observed in the Flemish Environment and Health Study.

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.