Search

Funding Information: This study was supported by the postdoctoral fellowship 2016/25853-4DN from Fundação de Amparo à Pesquisa do Estado de São Paulo (NK) . Funding Information: This study was supported by grant 217065/Z/19/Z from the UK Medical Research Council and Wellcome Trust and the University of Bristol (core support for the Avon Longitudinal Study of Parents and Children [ALSPAC]); Funding Information: This study was supported by the STOP project, which received grant 774548 from the European Union's Horizon 2020 research and innovation program. OR was supported by a UKRI Future Leaders Fellowship (MR/S03532X/1). CM and EV are funded by the National Institute for Health and Care Research School for Public Health Research, Grant Reference Number PD-SPH-2015. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. This study was supported by the postdoctoral fellowship 2016/25853-4DN from Fundação de Amparo à Pesquisa do Estado de São Paulo (NK). This study was supported by grant 217065/Z/19/Z from the UK Medical Research Council and Wellcome Trust and the University of Bristol (core support for the Avon Longitudinal Study of Parents and Children [ALSPAC]);, The collection of primary exposure and outcomes data in ALSPAC that were evaluated in this study were supported by grants 076467/Z/05/Z, 086676/Z/08/Z, 086684, 092731 and MC_UU_12013/1 from MRC, grant from Wellcome Trust, grants 5R01HL071248- 07, R01 DK077659 from NIH, grant from British Heart Foundation. A comprehensive list of grant funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grantacknowledgements. pdf). Funding Information: CM and EV are funded by the National Institute for Health and Care Research School for Public Health Research , Grant Reference Number PD-SPH-2015 . The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Funding Information: This study was supported by the STOP project , which received grant 774548 from the European Union's Horizon 2020 research and innovation program . Funding Information: The collection of primary exposure and outcomes data in ALSPAC that were evaluated in this study were supported by grants 076467/Z/05/Z , 086676/Z/08/Z , 086684 , 092731 and MC_UU_12013/1 from MRC , grant from Wellcome Trust , grants 5R01HL071248- 07 , R01 DK077659 from NIH , grant from British Heart Foundation . Funding Information: OR was supported by a UKRI Future Leaders Fellowship ( MR/S03532X/1 ). Publisher Copyright: © 2022 The Authors Background & aims: Higher consumption of ultra-processed foods (UPF) has been associated with childhood obesity, but underlying mechanisms remain unclear. We investigated plasma nuclear magnetic resonance metabolic profiles of higher UPF consumption and their role in obesity risk in the British ALSPAC cohort. Methods: We performed cross-sectional and prospective metabolome wide association analyses of UPF, calculated from food diaries using the NOVA classification. In cross-sectional analysis, we tested the association between UPF consumption and metabolic profile at 7 years (N = 4528), and in the prospective analysis we tested the association between UPF consumption at 13 years and metabolic profile at 17 years (N = 3086). Effects of UPF-associated metabolites at 7 years on subsequent fat mass accumulation were assessed using growth curve models. Results: At 7 years, UPF was associated with 115 metabolic traits including lower levels of branched-chain and aromatic amino acids and higher levels of citrate, glutamine, and monounsaturated fatty acids, which were also associated with greater fat mass accumulation. Reported intake of nutrients mediated associations with most metabolites, except for citrate. Conclusions: UPF consumption among British children is associated with perturbation of multiple metabolic traits, many of which contribute to child obesity risk. publishersversion published

The exposome represents an interdisciplinary science and promising field of research that can identify how multiple facets of the environment influences health across the lifespan. A particular sensitive and critical window for environmental exposures and exposure-associated health is during early life, especially childhood. Previous studies of the exposome during childhood are highlighted, including the external and internal exposome. Challenges, and potential ways to overcome them, of the childhood exposome are presented with the aims to improve exposome studies during early life.

Background: The mechanisms underlying childhood overweight and obesity are poorly known. Here, we investigated the direct and indirect effects of different prenatal exposures on offspring rapid postnatal growth and overweight in childhood, mediated through cord blood metabolites. Additionally, rapid postnatal growth was considered a potential mediator on childhood overweight, alone and sequentially to each metabolite. Methods: Within four European birth-cohorts (N = 375 mother-child dyads), information on seven prenatal exposures (maternal education, pre-pregnancy BMI, weight gain and tobacco smoke during pregnancy, age at delivery, parity, and child gestational age), selected as obesogenic according to a-priori knowledge, was collected. Cord blood levels of 31 metabolites, associated with rapid postnatal growth and/or childhood overweight in a previous study, were measured via liquid-chromatography-quadrupole-time-of-flight-mass-spectrometry. Rapid growth at 12 months and childhood overweight (including obesity) between four and eight years were defined with reference to WHO growth charts. Single mediation analysis was performed using the imputation approach and multiple mediation analysis using the extended-imputation approach. Results: Single mediation suggested that the effect of maternal education, pregnancy weight gain, parity, and gestational age on rapid postnatal growth but not on childhood overweight was partly mediated by seven metabolites, including cholestenone, decenoylcarnitine(C10:1), phosphatidylcholine(C34:3), progesterone and three unidentified metabolites; and the effect of gestational age on childhood overweight was mainly mediated by rapid postnatal growth. Multiple mediation suggested that the effect of gestational age on childhood overweight was mainly mediated by rapid postnatal growth and that the mediating role of the metabolites was marginal. Conclusion: Our findings provide evidence of the involvement of in utero metabolism in the propensity to rapid postnatal growth and of rapid postnatal growth in the propensity to childhood overweight. We did not find evidence supporting a mediating role of the studied metabolites alone between the studied prenatal exposures and the propensity to childhood overweight. This work is supported by the Bijzonder Onderzoeksfonds Hasselt University through a PhD fellowship [to RA], by the UKRI Future Leaders Fellowship [MR/S03532X/1, to OR] and by the European Commission Horizon 2020 Grant to the ‘STOP Project’ [Grant ref 774548]. The ENVIRONAGE birth cohort is supported by the European Research Council [ERC-2012-StG.310898], and by funds of the Flemish Scientific Research council [FWO, G.0.733.15.N]. The Piccolipiù cohort was initially supported by the Italian National Center for Disease Prevention and Control (CCM grants years 2010 and 2014) and by the Italian Ministry of Health (art 12 and 12 bis D.lgs 502/92). The Rhea study has been funded by various European grants since 2006 and by the Greek Ministry of Health. INMA data collections were supported by grants from the Instituto de Salud Carlos III, CIBERESP, and the Generalitat de Catalunya-CIRIT. ISGlobal acknowledges support from the Spanish Ministry of Science, Innovation and Universities, “Centro de Excelencia Severo Ochoa 2013-2017”, SEV-2012-0208, and “Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya” (2017SGR595).

We evaluated the epidemiological evidence on the built environment and its link to childhood obesity, focusing on environmental factors such as traffic noise and air pollution, as well as physical factors potentially driving obesity-related behaviors, such as neighborhood walkability and availability and accessibility of parks and playgrounds. Eligible studies were (i) conducted on human children below the age of 18 years, (ii) focused on body size measurements in childhood, (iii) examined at least one built environment characteristic, (iv) reported effect sizes and associated confidence intervals, and (v) were published in English language. A z test, as alternative to the meta-analysis, was used to quantify associations due to heterogeneity in exposure and outcome definition. We found strong evidence for an association of traffic-related air pollution (nitrogen dioxide and nitrogen oxides exposure, p

Childhood obesity has become a global epidemic and carries significant long-term consequences to physical and mental health. Metabolomics, the global profiling of small molecules or metabolites, may reveal the mechanisms of development of childhood obesity and clarify links between obesity and metabolic disease. A systematic review of metabolomic studies of childhood obesity was conducted, following Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines, searching across Scopus, Ovid, Web of Science and PubMed databases for articles published from January 1, 2005 to July 8, 2020, retrieving 1271 different records and retaining 41 articles for qualitative synthesis. Study quality was assessed using a modified Newcastle-Ottawa Scale. Thirty-three studies were conducted on blood, six on urine, three on umbilical cord blood, and one on saliva. Thirty studies were primarily cross-sectional, five studies were primarily longitudinal, and seven studies examined effects of weight-loss following a life-style intervention. A consistent metabolic profile of childhood obesity was observed including amino acids (particularly branched chain and aromatic), carnitines, lipids, and steroids. Although the use of metabolomics in childhood obesity research is still developing, the identified metabolites have provided additional insight into the pathogenesis of many obesity-related diseases. Further longitudinal research is needed into the role of metabolic profiles and child obesity risk.

The tremendous increase in childhood obesity prevalence over the last few decades cannot merely be explained by genetics and evolutionary changes in the genome, implying that gene-environment interactions, such as epigenetic modifications, likely play a major role. This systematic review aims to summarize the evidence of the association between epigenetics and childhood obesity. A literature search was performed via PubMed and Scopus engines using a combination of terms related to epigenetics and pediatric obesity. Articles studying the association between epigenetic mechanisms (including DNA methylation and hydroxymethylation, non-coding RNAs, and chromatin and histones modification) and obesity and/or overweight (or any related anthropometric parameters) in children (0-18 years) were included. The risk of bias was assessed with a modified Newcastle-Ottawa scale for non-randomized studies. One hundred twenty-one studies explored epigenetic changes related to childhood obesity. DNA methylation was the most widely investigated mechanism (N = 101 studies), followed by non-coding RNAs (N = 19 studies) with evidence suggestive of an association with childhood obesity for DNA methylation of specific genes and microRNAs (miRNAs). One study, focusing on histones modification, was identified. Heterogeneity of findings may have hindered more insights into the epigenetic changes related to childhood obesity. Gaps and challenges that future research should face are herein described.

Introduction Metabolomics may identify biological pathways predisposing children to the risk of overweight and obesity. In this study, we have investigated the cord blood metabolic signatures of rapid growth in infancy and overweight in early childhood in four European birth cohorts. Methods Untargeted liquid chromatography-mass spectrometry metabolomic profiles were measured in cord blood from 399 newborns from four European cohorts (ENVIRONAGE, Rhea, INMA and Piccolipiu). Rapid growth in the first year of life and overweight in childhood was defined with reference to WHO growth charts. Metabolome-wide association scans for rapid growth and overweight on over 4500 metabolic features were performed using multiple adjusted logistic mixed-effect models and controlling the false discovery rate (FDR) at 5%. In addition, we performed a look-up analysis of 43 pre-annotated metabolites, previously associated with birthweight or rapid growth. Results In the Metabolome-Wide Association Study analysis, we identified three and eight metabolites associated with rapid growth and overweight, respectively, after FDR correction. Higher levels of cholestenone, a cholesterol derivative produced by microbial catabolism, were predictive of rapid growth (p = 1.6 x 10(-3)). Lower levels of the branched-chain amino acid (BCAA) valine (p = 8.6 x 10(-6)) were predictive of overweight in childhood. The area under the receiver operator curve for multivariate prediction models including these metabolites and traditional risk factors was 0.77 for rapid growth and 0.82 for overweight, compared with 0.69 and 0.69, respectively, for models using traditional risk factors alone. Among the 43 pre-annotated metabolites, seven and five metabolites were nominally associated (P < 0.05) with rapid growth and overweight, respectively. The BCAA leucine, remained associated (1.6 x 10(-3)) with overweight after FDR correction. Conclusion The metabolites identified here may assist in the identification of children at risk of developing obesity and improve understanding of mechanisms involved in postnatal growth. Cholestenone and BCAAs are suggestive of a role of the gut microbiome and nutrient signalling respectively in child growth trajectories. This research was supported by European Commission Horizon 2020 Grant to the ‘STOP Project’ (Grant ref. 774548). This study was funded by the European Union Social Fund and the Hellenic Ministry of Health (“Programme of prevention and early diagnosis of obesity and neurodevelopment disorders in preschool-age children in the prefecture of Heraklion, Crete, Greece’ MIS number 349580, NSRF 2007-2013). Additional funding from the National Institute of Environmental Health Sciences (NIEHS) supported Dr. Chatzi (R01ES030691, R01ES029944, R01ES030364, R21ES029681, R21ES028903 and P30ES007048). The ENVIRONAGE birth-cohort is supported by the EU Program ‘Ideas’ (ERC-2012-StG-310898) and the FWO (G082317N), a PhD fellowship of the Bijzonder Onderzoeksfonds (BOF) at Hasselt University supported MD Alfano. We acknowledge support from the Spanish Ministry of Science, Innovation and Universities, ‘Centro de Excelencia Severo Ochoa 2013-2017”, SEV-2012-0208 and ‘Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya’ (2017SGR595). O.R. was supported by a UKRI Future Leaders Fellowship (MR/S03532X/1).

In this study, the exposome paradigm has been applied on a mother-child cohort adopting an optimised untargeted metabolomics approach for human urine followed by advanced bioinformatics analysis. Exposome-wide association algorithms were used to draw links between in utero co-exposure to metals and phthalates, metabolic pathways deregulation, and clinically observed phenotypes of neurodevelopmental disorders such as problems in linguistic, motor development and cognitive capacity. Children (n = 148) were tested at the first and second year of their life using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Their mothers had been exposed to metals and phthalates during the pregnancy, according to human biomonitoring results from previously performed studies. Untargeted metabolomics analysis of biobanked urine samples from the mothers was performed using a combination of the high throughput analytical methods liquid chromatography-high resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR). Most perturbed metabolic pathways from co-exposure heavy metals and phthalates were pathways related to the tricarboxylic acid cycle (TCA cycle) and oxidative phosphorylation, indicating the possibility of disruption of mitochondrial respiration. Overproduction of reactive oxygen species (ROS); the presence of glutathione peroxidase 3 (GPx3) during pregnancy and presence of glutathione peroxidase 1 (GPx1) in the umbilical cord were linked to verbal development problems. Another finding of the study is that in real life, adverse outcomes occur as a combination of environmental and social factors, all of them acting synergistically towards the deployment of an observed phenotype. Finally, the two-steps association process (exposure to pathways and pathways to adverse outcomes) was able to (a) provide associations that are not evident by directly associating exposure to outcomes and (b) provides additional insides on the mechanisms of environmental disease.

Trace element concentrations in biological fluids may vary according to the individual exposome, especially when considering specific external factors of the environment, such as occupational activities. The aim of this study was to determine concentrations of Potentially Toxic Elements (PTEs: As, Cr, Cd, Cu, Mn, Ni, Pb, Zn) in urine samples of informal jewelry workers and in jewelry and soldering powder. Fifty-two families from Brazil comprised the Exposed (n = 113) and Control (n = 79) groups. PTE concentrations in urine samples (n = 192) of workers, controls and their family members were determined by ICP-MS. Soldering powder samples (n = 7) and jewelry pieces (n = 54) were measured for PTEs by field-portable X-ray fluorescence. Levels of PTEs in urine and occupational exposure associations were determined. The environment-wide association study (EWAS) approach was applied to test the influence of occupational activities on participant exposure. Mean PTE concentrations were within the limits recommended in urine by Brazilian occupational guidelines. However, As, Cd, Ni and Zn concentrations in some samples exceeded acceptable values for environmental exposure in the U.S and Canada, as well as Brazilian occupational limits. Cd concentrations were higher for women (0.19 μg g−1 creatinine; p = 0.01), adult workers (0.25 μg g−1 creatinine; p = 0.0002) and smokers (0.27 μg g−1creatinine; p = 0.0001). The difference between the Exposed (0.17 μg g−1creat.) and Control groups (0.10 μg g−1creat.) for Cd was significant among non-smokers. Workers engaged in soldering and assemblers had higher Cd concentrations (0.61 and 0.18 μg g−1 creatinine, respectively) than individuals not working with jewelry production (0.12 μg g−1 creat). PTEs in some jewelry and all soldering powder exceeded Brazilian limits. Considering this exposure scenario, informal jewelry production increased urinary cadmium levels in workers. Occupational exposure to this element in the household environment should be explored, as it may pose a health risk to family members and workers alike.

The first Italian human biomonitoring survey (PROBE - PROgramme for Biomonitoring general population Exposure) considered a reference population of adolescents, aged 13-15 years, living in urban and rural areas and investigated their exposure to metals. The study was expanded up to 453 adolescents living in the same areas of Latium Region (Italy) and blood samples were analyzed for 19 metals (As, Be, Cd, Co, Cr, Hg, Ir, Mn, Mo, Ni, Pb, Pd, Pt, Rh, Sb, Sn, Tl, V, and W) by sector field inductively coupled plasma mass spectrometry. The exposure assessment was contextualized following an exposome approach that considered several determinants related to the subjects, available environmental parameters and geo-coding of residence address. To assess the influence of exposure determinants and modifiers on children biomarkers levels we used two independent methodologies. The first makes use of the so-called Environment-Wide Association Study (EWAS) methodology while the second was based on the application of a Generalized Liner Model (GLM) capturing co-exposures to pairs of key determinants. Based on our analysis, Hg and As were positively associated with dietary pathways (primarily linked to fish and to a lesser extent to milk consumption) while Cr showed a more complex interaction between co-exposure to different dietary pathways (milk and fish) coupled to proximity of residence to industrial activities. In addition to diet, socio-economic status of the mother revealed robust statistical associations with Cd, Ni and W biomonitoring levels in the respective children.

International audience; Background Metabolomics is the comprehensive study of a multitude of small molecules to gain insight into an organism's metabolism. The research field is dynamic and expanding with applications across biomedical, biotechnological, and many other applied biological domains. Its computationally intensive nature has driven requirements for open data formats, data repositories, and data analysis tools. However, the rapid progress has resulted in a mosaic of independent, and sometimes incompatible, analysis methods that are difficult to connect into a useful and complete data analysis solution. Findings PhenoMeNal (Phenome and Metabolome aNalysis) is an advanced and complete solution to set up Infrastructure-as-a-Service (IaaS) that brings workflow-oriented, interoperable metabolomics data analysis platforms into the cloud. PhenoMeNal seamlessly integrates a wide array of existing open-source tools that are tested and packaged as Docker containers through the project's continuous integration process and deployed based on a kubernetes orchestration framework. It also provides a number of standardized, automated, and published analysis workflows in the user interfaces Galaxy, Jupyter, Luigi, and Pachyderm. Conclusions PhenoMeNal constitutes a keystone solution in cloud e-infrastructures available for metabolomics. PhenoMeNal is a unique and complete solution for setting up cloud e-infrastructures through easy-to-use web interfaces that can be scaled to any custom public and private cloud environment. By harmonizing and automating software installation and configuration and through ready-to-use scientific workflow user interfaces, PhenoMeNal has succeeded in providing scientists with workflow-driven, reproducible, and shareable metabolomics data analysis platforms that are interfaced through standard data formats, representative datasets, versioned, and have been tested for reproducibility and interoperability. The elastic implementation of PhenoMeNal further allows easy adaptation of the infrastructure to other application areas and omics research domains.

The current study aims at a comprehensive risk characterization of bisphenol A (BPA) supported by an integrated exposure modelling framework that comprises far field and near field exposure modelling coupled to a dynamic lifetime PBTK model. Exposure analysis was done on European data of BPA food residues and human biomonitoring (HBM). The latter were further assimilated through an advanced exposure reconstruction modelling framework to estimate the corresponding external and internal systemic dose of BPA and its metabolites. Special attention was paid on the assessment of exposure to BPA during critical developmental stages such as gestation by modelling the mother-fetus toxicokinetic interaction. Our findings showed that current exposure levels in Europe are below the temporary Tolerable Daily Intake (t-TDI) of 4 μg/kg_bw/d proposed by the European Food Safety Authority. Taking into account age-dependent bioavailability differences, internal exposure of premature neonates hosted in intensive care units was reckoned close to the biologically effective dose (BED) resulting from translating the EFSA temporary total daily intake (t-TDI) into equivalent internal dose. Use of the ToxCast21 Biological Pathway Altering Dose (BPAD) as an alternative internal exposure reference value, resulted in increased margins of safety compared to the conventional exposure/risk characterization scheme.

To date, landfilling remains the most common waste management practice in Greece in spite of enforced regulations aiming at increasing recycling, pre-selection of waste and energy and material recovery. In this study, selected alternative scenarios aiming at minimizing the unused material fraction to be disposed of in landfills are analyzed, using the life cycle assessment methodology. The methodology was applied in the case of municipal solid waste (MSW) management in Athens and Thessaloniki, with a special focus on energy and material balance, including potential global and local scale airborne emissions. Results are given in the form of indices efficiency, effectiveness, environmental and public health impacts. Material flow accounting, gross energy requirement, emergy intensity, emission and release intensity and morbidity or mortality indicators have been used to support the comparative assessment. However, not all options are equally benign to the local environment and to the health of the local population, since both the former and the latter are still affected by non-negligible local emissions. With regard to public health impacts, adverse effects on respiratory health, congenital malformations, low birth weight and cancer incidence were estimated. A significant and not intuitive result is the fact that life cycle analysis produces different conclusions than a simple environmental impact assessment based only on estimated or measured emissions. Taking into account the overall life cycle of both the waste streams and of the technological systems and facilities envisaged alters the relative attractiveness of the solutions considered.

The current study within the frame of the HEALS project aims at the development of a lifelong physiologically based biokinetic (PBBK) model for exposome studies. The aim was to deliver a comprehensive modelling framework for addressing a large chemical space. Towards this aim, the delivered model can easily adapt parameters from existing ad-hoc models or complete the missing compound specific parameters using advanced quantitative structure activity relationship (QSAR). All major human organs are included, as well as arterial, venous, and portal blood compartments. Xenobiotics and their metabolites are linked through the metabolizing tissues. This is mainly the liver, but also other sites of metabolism might be considered (intestine, brain, skin, placenta) based on the presence or not of the enzymes involved in the metabolism of the compound of interest. Each tissue is described by three mass balance equations for (a) red blood cells, (b) plasma and interstitial tissue and (c) cells respectively. The anthropometric parameters of the models are time dependent, so as to provide a lifetime internal dose assessment, as well as to describe the continuously changing physiology of the mother and the developing fetus. An additional component of flexibility is that the biokinetic processes that relate to metabolism are related with either Michaelis-Menten kinetics, as well as intrinsic clearance kinetics. The capability of the model is demonstrated in the assessment of internal exposure and the prediction of expected biomonitored levels in urine for three major compounds within the HEALS project, namely bisphenol A (BPA), Bis(2-ethylhexyl) phthalate (DEHP) and cadmium (Cd). The results indicated that the predicted urinary levels fit very well with the ones from human biomonitoring (HBM) studies; internal exposure to plasticizers is very low (in the range of ng/L), while internal exposure to Cd is in the range of μg/L.

The city of Limeira presents a relevant productive chain of jewelry and fashion jewelry, including a scenario of outsourcing informal home practices. It is highly complex to understand the potentially toxic elements (PTE: Cr, Mn, Ni, Cu, Zn, As, Cd, Sn, Sb, Hg, and Pb) exposures of the workers because this productive chain encompasses households. This study aimed to investigate the associations between blood PTE levels and informal work in the home environment. Fifty-two families divided into Exposed group (n = 112) and Control group (n = 53) were included. Families' blood (n = 165) and welder's breathing zone air samples (n = 9) were collected and PTEs concentrations were determined by ICP-MS. Questionnaires were applied to collect sociodemographic information and workplace details. Principal component analysis, Mann-Whitney test, cluster and a logistic regression analysis based on environment-wide association studies (EWAS) were carried out. Ni, Cu, Zn, Cd and Pb concentrations in the air samples were higher than occupational guidelines. Eighty percent of the workers were female, and 43.5% of those females then worked as welder. A significant difference was found for Pb concentration between the exposed and control group (p 0.0001) and between sexes (p = 0.0046). For Cu (p 0.0001) and Sb (p = 0.0434), differences were found between the sexes. The receiver operating characteristic of the EWAS was 0.80, providing evidence of a potential model to associate exposure levels and occupational factors. PTEs concentrations in the air samples raised concerns, particularly for children, who were in the same exposure scenario. Inadequate work conditions were observed in the houses, revealing the need of public actions to protect these families.

This chapter aims at outlining the current state of science in the field of computational exposure biology and in particular at demonstrating how the bioinformatics techniques and algorithms can be used to support the association between environmental exposures and human health and the deciphering of the molecular and metabolic pathways of induced toxicity related to environmental chemical stressors. Examples of the integrated bioinformatics analyses outlined herein are given concerning exposure to airborne chemical mixtures, to organic compounds frequently found in consumer goods, and to mixtures of organic chemicals and metals through multiple exposure pathways. Advanced bioinformatics are coupled with big data analytics to perform studies of exposome-wide associations with putative adverse health outcomes. In conclusion, the chapter gives the reader an outline of the available computational tools and paves the way towards the development of future comprehensive applications that are expected to support efficiently exposome research in the 21st century.

This chapter provides a comprehensive overview of the state of the art and beyond regarding modelling and data analytics towards refined external and internal exposure assessment, for elucidating the human exposome. This includes methods for more accurate measurement of personal exposure (using wearable sensors) and for extrapolation to larger population groups (agent-based modelling). A key component in the modern risk and health impact assessment is the translation of external exposure into internal exposure metrics, accounting for age, gender, genetic and route of exposure dependent differences. The applicability of biokinetics covering a large chemical space is enhanced using quantitative structure activity relationships, especially when the latter are estimated using machine learning tools. Finally, comprehensive biomonitoring data interpretation and assimilation are supported by exposure reconstruction algorithms coupled with biokinetics

Charilaos Trikoupis bridge is the longest cable bridge in Europe that connects Western Greece with the rest of the country. In this study, six air pollution monitoring campaigns (including major regulated air pollutants) were carried out from 2013 to 2015 at both sides of the bridge, located in the urban areas of Rio and Antirrio respectively. Pollution data were statistically analyzed and air quality was characterized using US and European air quality indices. From the overall campaign, it was found that air pollution levels were below the respective regulatory thresholds, but once at the site of Antirrio (26.4 and 52.2 μg/m 3 for PM 2.5 and ΡΜ 10 , respectively) during the 2nd winter period. Daily average PM 10 and PM 2.5 levels from two monitoring sites were well correlated to gaseous pollutant (CO, NO, NO 2 , NO x and SO 2 ) levels, meteorological parameters and factor scores from Positive Matrix Factorization during the 3-year period. Moreover, the elemental composition of PM 10 and PM 2.5 was used for source apportionment. That analysis revealed that major emission sources were sulfates, mineral dust, biomass burning, sea salt, traffic and shipping emissions for PM 10 and PM 2.5 , for both Rio and Antirrio. Seasonal variation indicates that sulfates, mineral dust and traffic emissions increased during the warm season of the year, while biomass burning become the dominant during the cold season. Overall, the contribution of the Charilaos Trikoupis bridge to the vicinity air pollution is very low. This is the result of the relatively low daily traffic volume (~ 10,000 vehicles per day), the respective traffic fleet composition (~ 81% of the traffic fleet are private vehicles) and the speed limit (80 km/h) which does not favor traffic emissions. In addition, the strong and frequent winds further contribute to the rapid dispersion of the emitted pollutants.

The current study aims at a comprehensive risk characterization of bisphenol A (BPA) supported by an integrated exposure modelling framework that comprises far field and near field exposure modelling coupled to a dynamic lifetime PBTK model. Exposure analysis was done on European data of BPA food residues and human biomonitoring (HBM). The latter were further assimilated through an advanced exposure reconstruction modelling framework to estimate the corresponding external and internal systemic dose of BPA and its metabolites. Special attention was paid on the assessment of exposure to BPA during critical developmental stages such as gestation by modelling the mother-fetus toxicokinetic interaction. Our findings showed that current exposure levels in Europe are below the temporary Tolerable Daily Intake (t-TDI) of 4 μg/kg_bw/d proposed by the European Food Safety Authority. Taking into account age-dependent bioavailability differences, internal exposure of premature neonates hosted in intensive care units was reckoned close to the biologically effective dose (BED) resulting from translating the EFSA temporary total daily intake (t-TDI) into equivalent internal dose. Use of the ToxCast21 Biological Pathway Altering Dose (BPAD) as an alternative internal exposure reference value, resulted in increased margins of safety compared to the conventional exposure/risk characterization scheme

The objective of the INTEGRA project is to bring together all information necessary for assessing the source-to-dose exposure continuum over the entire life cycle of substances covering an extensiv...

Markers of biological aging have potential utility in primary care and public health. We developed a model of age based on untargeted metabolic profiling across multiple platforms, including nuclear magnetic resonance spectroscopy and liquid chromatography–mass spectrometry in urine and serum, within a large sample (N = 2,239) from the UK Airwave cohort. We validated a subset of model predictors in a Finnish cohort including repeat measurements from 2,144 individuals. We investigated the determinants of accelerated aging, including lifestyle and psychological risk factors for premature mortality. The metabolomic age model was well correlated with chronological age (mean r = .86 across independent test sets). Increased metabolomic age acceleration (mAA) was associated after false discovery rate (FDR) correction with overweight/obesity, diabetes, heavy alcohol use and depression. DNA methylation age acceleration measures were uncorrelated with mAA. Increased DNA methylation phenotypic age acceleration (N = 1,110) was associated after FDR correction with heavy alcohol use, hypertension and low income. In conclusion, metabolomics is a promising approach for the assessment of biological age and appears complementary to established epigenetic clocks., We have developed a novel assessment of biological age using broad metabolomic profiling of small molecules circulating in blood and urine, collected from over 2,000 working age adults. We compare this metabolomic age assessment with an established epigenetic ‘clocks’ and show that ‘age acceleration’ is associated with risk factors of premature mortality, including depression.