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Forns J.,Norwegian Institute of Public Health | Mandal S.,Norwegian Institute of Public Health | Iszatt N.,Norwegian Institute of Public Health | Polder A.,Norwegian University of Life Sciences | And 5 more authors.
Environmental Research | Year: 2016

Background The aim of this study was to assess the association between postnatal exposure to multiple persistent organic pollutants (POPs) measured in breast milk samples and early behavioral problems using statistical methods to deal with correlated exposure data. Methods We used data from the Norwegian HUMIS study. We measured concentrations of 24 different POPs in human milk from 612 mothers (median collection time: 32 days after delivery), including 13 polychlorinated biphenyls (PCB) congeners, 6 polybrominated diphenyl ethers (PBDE) congeners and five organochlorine compounds. We assessed child behavioral problems at 12 and 24 months using the infant toddler symptom checklist (ITSC). Higher score in ITSC corresponds to more behavioral problems. First we performed principal component analysis (PCA). Then two variable selection methods, elastic net (ENET) and Bayesian model averaging (BMA), were applied to select any toxicants associated with behavioral problems. Finally, the effect size of the selected toxicants was estimated using multivariate linear regression analyses. Results p,p′-DDT was associated with behavioral problems at 12 months in all the applied models. Specifically, the principal component composed of organochlorine pesticides was significantly associated with behavioral problems and both ENET and BMA identified p,p′-DDT as associated with behavioral problems. Using a multiple linear regression model an interquartile increase in p,p′-DDT was associated with a 0.62 unit increase in ITSC score (95% CI 0.45, 0.79) at 12 months, corresponding to more behavioral problems. The association was modified by maternal education: the effect of p,p′-DDT was strongest in women with lower education (β=0.59; 95%CI: 0.38, 0.81) compared to the mother with higher education (β=0.14; 95%CI: −0.05, 0.34) (p-value for interaction=0.089). At 24 months, neither selection method consistently identified any toxicant associated with behavioral problems. Conclusion Within a mixture of 24 toxicants measured in breast milk, p,p′-DDT was the single toxicant associated with behavioral problems at 12 months using different methods for handling numerous correlated exposures. © 2016 Elsevier Inc. Source


Rava M.,Center for Research in Epidemiology and Population Health | Rava M.,University Paris - Sud | Smit L.A.M.,Institute for Risk Assessment science IRAS | Nadif R.,Center for Research in Epidemiology and Population Health | Nadif R.,University Paris - Sud
Current Opinion in Allergy and Clinical Immunology | Year: 2015

Purpose of Review: Asthma is a complex disease characterized by an intricate interplay of both heritable and environmental factors. Understanding the mechanisms through which genes and environment interact represents one of the major challenges for pulmonary researchers. This review provides an overview of the recently published literature on gene-environment (G×E) interactions in asthma, with a special focus on the new methodological developments in the postgenomewide association studies (GWAS) era. Recent Findings: Most recent studies on G×E interaction in asthma used a candidate-gene approach. Candidate-gene studies considering exposure to outdoor air pollutants showed significant interactions mainly with variants in the GSTP1 gene on asthma in children. G×E studies on passive and active smoking, including one genomewide interaction study, identified novel genes of susceptibility to asthma and a time-dependent effect of maternal smoking. Other recent studies on asthma found interactions between candidate genes and occupational allergen exposure and several domestic exposures such as endotoxin and gas cooking. New methods were developed to efficiently estimate G×E interaction in GWAS, and a pathway-based strategy to select an enriched gene-set for G×E studies has recently been proposed. Summary: The G×E studies presented in this review offer a good example on how candidate-gene approaches can complement and help in validating GWAS findings. © 2015 Wolters Kluwer Health, Inc. All rights reserved. Source


Grant
Agency: Narcis | Branch: Project | Program: Completed | Phase: Agriculture | Award Amount: | Year: 1997

None


Grant
Agency: Narcis | Branch: Project | Program: Completed | Phase: Agriculture | Award Amount: | Year: 2007

The main goal of this project is to find a proper measure of exposure characterising extremely low frequency (ELF) and radiofrequency (RF) exposure, for usage in epidemiological studies to define high vs low exposed persons or in human experimental studies to use realistic every (whole) day exposure values. Exposure occurs at different spatial and temporal levels: micro-, meso- and macro-level. In order to compare exposure at these levels a measure of exposure should be defined at each level. Preferably, the measure of exposure is expressed as a single number.The secondary goal is to build an exposure classification system, for instance by means of an Activity Exposure Matrix (AEM), which couples an activity to a level of exposure. The AEM is filled with the single digit characterisation based on personal exposimeter data. Ideally, in future research the exposure can be estimated based on a combination of this AEM and a questionnaire, without the need to actually measure. Or it can be used in epidemiological studies to select suitable contrast (high-low exposed) activities and groups of persons performing these activities.An additional aim is the creation of a database/inventory of the current exposure situation in the Netherlands. This database is preferably an extension of the current RIVM GIS system containing the major transmitters for radio and TV and the base stations.To achieve the project s goal the following research questions are formulated:1. What is a proper measure of exposure, based on measurements?2. What activities lead to high and what activities to low exposure?3. Can a questionnaire on activity patterns discriminate between high and low exposed groups?4. What is the exposure contrast in the Netherlands? Exposure characterisation is an essential part of research into the possible health effects due to exposure of radiofrequency electromagnetic fields. Because the mechanism which describes the steps from exposure to possible health effect is unknown, the relevant measure of exposure is also unknown. This project contributes to the development of tools and models that allow a better characterisation of exposure in epidemiological studies and in specific work situations. The project also gives a better insight into what characteristics of exposure are important and how they are represented in the populations studied. This project intends to develop methods to produce valid estimates of exposure due to sources in the living environment, like mobile phone base stations (GSM, DCS and UMTS) and sources used close to individuals (mobile phone, DECT and Wifi) and due to several sources in the workplace. The main goal of this project is to find a proper measure of exposure characterising extremely low frequency (ELF) and radiofrequency (RF) exposure, for usage in epidemiological studies to define high vs low exposed persons or in human experimental studies to use realistic every (whole) day exposure values. Exposure occurs at different spatial and temporal levels: micro-, meso- and macro-level. In order to compare exposure at these levels a measure of exposure should be defined at each level. Preferably, the measure of exposure is expressed as a single digit.The secondary goal is to build an exposure classification system, for instance by means of an Activity Exposure Matrix (AEM), which couples an activity to a level of exposure. The AEM is filled with the single digit characterisation based on personal exposimeter data. Ideally, in future research the exposure can be estimated based on a combination of this AEM and a questionnaire, without the need to actually measure. Or it can be used in epidemiological studies to select suitable contrast (high-low exposed) activities and groups of persons performing these activities.An additional aim is the creation of a database/inventory of the current exposure situation in the Netherlands. This database is preferably an extension of the current RIVM GIS system containing the ma


Grant
Agency: Narcis | Branch: Project | Program: Completed | Phase: Physics, Chemistry and Medicine | Award Amount: | Year: 2008

1. To define the applicability domain of EST by testing a series of selected relevant classes of chemicals.2. To improve the prediction model of the EST on the basis of the results of testing the chemical classes as mentioned above and on the basis of the biology of the model.3. To enhance the predictivity and extrapolation to the human by investigating the possibility to use alternative differentiation routes and existing human stem cell lines.4. To feed the project outcome into the scientific community and into international regulatory bodies that deal with testing strategies and guidelines (EU, OECD) The Embryonic Stem cell Test (EST) is the most extensively studied animal-free alternative for developmental toxicity testing. Current experience with the EST indicates that the applicability domain and the prediction model require further study before implementation of EST in testing strategies can be considered. We will test a series of selected classes of compounds which are of relevance in view of existing knowledge on their developmental toxicity profile. Using the data generated, the prediction model will be improved, and the optimal place of EST in the reproductive toxicity testing strategy defined.In addition, a parallel approach is aimed at improvement of the predictivity of the test in the long term by exploring alternative stem cell differentiation routes and by using existing human rather than murine ES cell lines. Finally, the outcome will be continuously communicated in existing international bodies such as EU and OECD to promote implementation of the updated EST in international testing strategies.

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