No description available.

No / Developmental periods in early life may be particularly vulnerable to impacts of environmental exposures. Human research on this topic has generally focused on single exposure–health effect relationships. The “exposome” concept encompasses the totality of exposures from conception onward, complementing the genome. Objectives: The Human Early-Life Exposome (HELIX) project is a new collaborative research project that aims to implement novel exposure assessment and biomarker methods to characterize early-life exposure to multiple environmental factors and associate these with omics biomarkers and child health outcomes, thus characterizing the “early-life exposome.” Here we describe the general design of the project. Methods: In six existing birth cohort studies in Europe, HELIX will estimate prenatal and postnatal exposure to a broad range of chemical and physical exposures. Exposure models will be developed for the full cohorts totaling 32,000 mother–child pairs, and biomarkers will be measured in a subset of 1,200 mother–child pairs. Nested repeat-sampling panel studies (n = 150) will collect data on biomarker variability, use smartphones to assess mobility and physical activity, and perform personal exposure monitoring. Omics techniques will determine molecular profiles (metabolome, proteome, transcriptome, epigenome) associated with exposures. Statistical methods for multiple exposures will provide exposure–response estimates for fetal and child growth, obesity, neurodevelopment, and respiratory outcomes. A health impact assessment exercise will evaluate risks and benefits of combined exposures. Conclusions: HELIX is one of the first attempts to describe the early-life exposome of European populations and unravel its relation to omics markers and health in childhood. As proof of concept, it will form an important first step toward the life-course exposome.

Thesis (Ph. D.)--University of Texas Health Science Center at Houston, School of Public Health, 2006. / Includes bibliographical references (leaves 100-107).

Countries seek to control exposure to hazardous substances and environments by the enactment of legislation. In the past thirty years, two major different approaches to occupational health and safety legislation have been devleoped by countries around the world. The performance-based legislative approach has been linked with the emergence of occupational health and safety management systems but no research has previously been done to determine whether or not the legislative approach taken by government influences the introduction or form of occupational health and safety management systems used by organisations. Similarly, although the reasons why Australia and other countries have moved to performance-based legislation have been explained in terms of social, political and economic factors that influenced the change, little research has been done on the effectiveness of this approach compared with the prescriptive approach of countries such as Korea. -I- The overall aim of this research is to develop a conprehensive understanding of the management of expusre to heavy metals in selected industries in Korea and Australia. The specific objectives of the study are to determine: The effectiveness of heavy metal exposure management in the fluorescent lamp manufacturing industry in Korea, and an Oral Health Service, and lead-risk workplaces in Queensland, Australia; The management of the legislative arrangements for health surveillance in Korea and Queensland, Australia; The characteristics of the occupational health and safety management systems that are in use in the heavy metal industries in Korea in Australia; and The effectiveness of prescriptive and performance based legislative systems in protecting the health and safety of workers in heavy metal based industries. Secondary analysis of biological monitoring data from 6 fluorescent lamp manufacturing companies (8 workplaces) in Korea was used to examine the extent of mercury exposure and the effectiveness of the health surveillance system in that country. A survey of dental workers in an oral health service in Queensland provided data on the extent of mercury exposure to the workforce and workers' attitudes to the management of occupational risks. The efficiency of the lead health surveillance in Queensland was examined by way of a questionnaire survey of lead designated doctors in the state. A survey of registered lead-risk companies and the oral health servies in Queensland, and 5 of the fluorescent lamp manufacturing companies in Korea provided data on the occupational health and safety management systems in place in these organisations. The health surveillance system for mercury exposed workers in Korea was found to have reduced the incidence of workers with biological levels of mercury above the Baseline Level from 14% in 1994 to 7% in 1999. Bilogical testing of dental workers in Queensland discovered no workers with biological levels of mercury approaching the Baseline Level and air monitoring failed to locate any areas where workers were likely to be exposed to levels approaching the Workplace Exposure Standard. The staff of the Oral Health Service were generally aware of the occupational health and safety management systems in place but only 43% felt that mercury management in the workplace effectively prevented exposure. The lead surveillance system in Queensland was found to be inadequately managed with approximately 37% of registered doctors no longer practicing in the field and their being no way for the government to collect reliable data on the extent of lead exposure in workplaces. The occupational health and safety management systems in the companies surveyed in Queensland and Korea were found to be influenced by the legislative arrangements in place in each of the locations. The Korean systems were more geared to meeting the regulatory requirements whereas the Queensland systems were geared more towards a risk management approach. However substantial differences were also noted depending on the size of the organisation in each case. Legislative arrangements in Korea and Queensland were found to provide reasonable protection from heavy metal exposure to workers however improvements in both systems are needed. The legislation was also found to influence the occupational health and safety management systems in place with performance-based legislation producing systems having a wide risk management focus while a narrower regulatory based focus was noted in Korea where more prescriptive legislation is in force. A confounding factor in the nature of the occupational health and safety management system in place is the size of the organisation and particular attention needs to be paid to this when legislative approaches are considered.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

The first part of this dissertation, entitled Exchange Rate Exposure Management, addressed the question whether there has been a relationship between changes in exchange rate volatility and financial results of Czech enterprises and therefore foreign exchange exposure management is justified. For this purpose, the empirical data of revenues and exports and imports in CZ-NACE sections were used. Statistically significant results were demonstrated in the Section C - Manufacturing, where it was confirmed that profitability of sales declines with increasing volatility of the exchange rate. The nominal exchange rate CZK/EUR was taken into consideration, while a recent thesis (Klecka, 2016) showed that the use of another type of the exchange rate does not provide a statistically significant difference. In the second part a simple model called Estart was created in order to quantify the maximum impact of unexpected exchange rate changes in the profitability of a company and thus in order to start with the management of the exchange rate exposure. The formula for calculating exchange rate exposure is simple and requires only a few inputs as company total revenues, total expenses, the percentage of revenues in foreign currency and the percentage of expenditure in foreign currency. In order to quantify the maximum impact recommended percentage variations dependent on the time horizon were determined from the historical data of the exchange rate CZK/EUR. The company then receives initial information about the maximum impact of unexpected exchange rate change on their profitability and hence for example the potential maximum amount that makes sense to invest in exchange rate hedging. The model is also suitable for calculating the maximum impact for the specific payables and receivables. The Model Estart is for its simplicity usable particularly in small and medium-sized enterprises, which currently begin to address the question of the impact of exchange rate change on their profitability for example because of announcements of Czech National Bank concerning the end of the intervention that has been depreciating domestic currency since 2013 and also the complicated situation in the Eurozone. The next necessary step is to use more sophisticated methods in accordance with the principles of foreign exchange rate exposure management in order to quantify the impact of unexpected changes in the exchange rate on the profitability, respectively on the value of the company, mainly because of the management of the operational exposure, which is crucial and which is not addressed by this simple model.

Le cancer du sein est le cancer le plus fréquent chez la femme et son incidence a doublé ces 30 dernières années. Les facteurs environnementaux à effet perturbateur endocrinien, tels que les dioxines émises par les activités de combustion industrielle, sont suspectés d'augmenter le risque de cancer du sein. L'alimentation et l'inhalation sont les deux voies majeures d'exposition aux dioxines chez l'Homme. Les données épidémiologiques sur le sujet sont non concluantes, et il existe des limites méthodologiques. Ce travail doctoral avait pour objectif d'étudier l'impact de l'exposition aux dioxines sur le risque de cancer du sein dans la cohorte E3N, en répondant aux limites des études existantes.Nous avons évalué l'exposition alimentaire aux dioxines puis estimé le risque de cancer du sein associé parmi les femmes de la cohorte E3N. Nous avons ensuite développé un score d'exposition basé sur un système d'information géographique, associant la distance à la source, la durée d'exposition et la fréquence de vent dominant, afin d'évaluer l'exposition environnementale aux dioxines à chaque adresse des femmes entre 1990 et 2008. Le risque de cancer du sein associé au score d'exposition cumulé a été estimé dans une étude cas-témoins nichée dans la cohorte E3N, parmi les femmes ayant résidé en Rhône-Alpes. Aucune association n'a été observée, à l'exception d'une diminution du risque de cancer du sein hormono-indépendant, retrouvée de façon significative dans l'étude alimentaire. Cette dernière observation est cohérente avec des données expérimentales. Dû à un manque de puissance statistique pour l'exposition aérienne, nos résultats demandent confirmation au niveau national / Breast cancer (BC) is the first malignancy among women. Its incidence has doubled over the past 30 years. Environmental factors with endocrine disruptive properties, such as dioxins emitted from industrial combustion processes, are suspected to affect BC risk. Ingestion of contaminated food and inhalation are the major exposure routes in humans. Epidemiological evidence on the association between dioxin exposure and BC risk remains inconclusive due to methodological limitations. The aim of the thesis was to investigate the association between dioxin exposure and BC risk in the E3N prospective cohort, filling current methodological gaps.First, we assessed the association between estimated dietary dioxin exposure and BC risk among women from the E3N cohort. Second, we developed a geographic information system (GIS)-based metric to assess airborne dioxin exposure at the individual address level, including proximity to and technical characteristics of industrial sources, exposure duration and prevailing wind frequency. The metric was then applied to each E3N women’s addresses from 1990 to 2008, and airborne dioxin exposure was estimated for cases and matched controls from a cohort sub-population (the Rhône-Alpes region). Third, we estimated BC risk associated with cumulative airborne dioxin exposure. Overall, no statistically significant association was observed, except for a decrease in hormone-independent BC risk. The latter was significant for dietary dioxin exposure. For airborne exposure, we might have lacked statistical power and confirmation at the national level is required. The inverse association with ER-negative BC risk is consistent with experimental evidence

Les tumeurs germinales du testicule (TGT) représentent le cancer le plus fréquent chez les hommes Européens âgés de 15 et 39 ans. L'incidence a doublé dans la plupart des pays Européens depuis 30 ans. Cette augmentation rapide, les variations géographiques d'incidence et les études chez les populations migrantes suggèrent un rôle des facteurs environnementaux dans le développement des TGT. Cette thèse propose de contribuer à l'amélioration des connaissances concernant l'évolution du TGT en clarifiant l'impact des expositions environnementales et professionnelles, notamment pendant la période prénatale. Les objectifs principaux sont de: 1. Prédire l'incidence du TGT jusqu'en 2025 en estimant la part d'augmentation due aux changements démographiques afin d'obtenir une estimation de l'augmentation due aux risques. 2. Faire un bilan de l'état des connaissances sur l'association entre les expositions environnementales et professionnelles et le développement du TGT dans une revue systématique de littérature 3. Investiguer l'association entre l'exposition parentale professionnelle aux pesticides en période prénatale et le TGT parmi la descendance Les résultats montrent que l'incidence du TGT continue d'augmenter, mettant en avant un fort impact environnemental dans l'évolution du TGT. Néanmoins, la revue de littérature ne permettait pas d'identifier de facteurs de risque environnementaux avérés, mais montrait un manque d'études investiguant les expositions prénatales sur le risque de TGT. L'étude NORD-TEST menée sur les données de registre de quatre pays nordiques est l'étude la plus puissante à ce jour et ne montre aucune association entre l'exposition parentale professionnelle aux pesticides en période prénatale et le TGT / Testicular germ cell tumours (TGCT) are the most common cancer diagnosed among young European men aged between 15 and 39 years. TGCT incidence rates have doubled in most European countries over the last 30 years. This rapid increase in incidence, the geographical variations and the studies in migrant populations suggest a role of environmental factors in TGCT aetiology. This thesis aims to contribute to the knowledge of TGCT evolution by studying the impact of environmental and occupational exposures, especially during the prenatal period. The objectives are: 1. To estimate the proportion of the increased incidence due to overall changes in risk patterns compared to the proportion due to demographic changes, by predicting the future testicular cancer trends in Europe 2. To summarize and evaluate the current knowledge on environmental and occupational exposures related to TGCT risk by means of a systematic literature review 3. To investigate the association between the prenatal parental occupational exposure to pesticides and TGCT risk in the offspring. The results show that the TGCT incidence continues to increase, supporting an environmental impact on TGCT evolution. From the epidemiological literature to date no specific environmental risk factors emerge; however, there have clearly been a lack of studies investigating prenatal exposures on TGCT risk. The NORD-TEST study, based on registry data from four Nordic countries, is the largest study to date. No association was found between parental occupational exposure to pesticides during prenatal period and TGCT risk

No description available.

La mesure du bisphénol-S (BPS) et de son glucurono-conjugué (BPSG) dans l’urine peut être utilisée pour la biosurveillance de l’exposition dans les populations. Cependant, cela nécessite une connaissance approfondie de la toxicocinétique de ces composés alors qu’à ce jour, il existe peu de données à cet effet chez l’humain. L’évolution dans le temps du BPS et du BPSG a été évaluée dans des matrices biologiques accessibles et représentatives comme l`urine et le sang de volontaires exposés par voie orale et cutanée. Suite à l’approbation du comité d’éthique de la recherche de l’Université de Montréal, six volontaires ont été exposés par voie orale à une dose deutérée de BPS-d8 de 0,1 mg/kg de poids corporel. Un mois plus tard, 1 mg/kg pc de BPS-d8 ont été appliqués sur 40 cm2 de l’avant-bras puis lavés 6 h après l’application. Des échantillons de sang ont été prélevés avant le dosage et à des intervalles de temps fixes sur une période de 48 h après traitement ; des collectes urinaires complètes ont été recueillies avant l’exposition et à des intervalles préétablis sur 72 h après dosage. Après exposition par voie orale, les profils temporels des concentrations plasmatiques de BPS-d8 et de BPSG-d8 évoluaient en parallèle et ont montré une apparition et une élimination rapides. Les valeurs maximales de BPS-d8 et BPSG-d8 dans le plasma ont été atteintes en moyenne (± écart-type [ET]) à 0,7 ± 0,1 et 1,1 ± 0,4 h après le dosage et les demi-vies d’élimination apparentes (moyenne ± ET) (t ½) de 7,9 ± 1,1 et 9,3 ± 7,0 h ont été calculées à partir de la phase terminale, respectivement. La fraction de BPS-d8 atteignant la circulation systémique inchangée (c’est-à-dire la biodisponibilité) a en outre été estimée à 62 ± 5 % en moyenne (± ET) et la clairance plasmatique systémique à 0,57 ± 0,07 L/kg pc/h. Toujours après exposition orale, les profils temporels des taux d’excrétion urinaire évoluaient aussi de manière parallèle aux concentrations plasmatiques et étaient similaires pour tant pour le composé parent que le métabolite. Le pourcentage moyen (± ET) de la dose administrée récupérée dans l’urine sous forme de BPS-d8 et BPSG-d8 au cours de la période de 72 h après le dosage était de 1,72 ± 1,3 et 54 ± 10 %. Après application cutanée, les niveaux plasmatiques étaient inférieurs à la limite inférieure de quantification (LLOQ) à la plupart des points dans le temps. Cependant, les valeurs maximales étaient atteintes entre 5 et 8 h selon les individus, suggérant un taux d’absorption plus lent par rapport à l’exposition orale. De même, des quantités limitées de BPS-d8 et de son conjugué, estimées en pourcentage de dose, de l’ordre 0,004 ± 0,003 et 0,09 ± 0,07 %. En somme, cette étude a fourni une plus grande précision sur la cinétique du BPS chez l’humain. Ces données seront utiles pour développer un modèle toxicocinétique pour une meilleure interprétation des données de biosurveillance. Pour la voie orale, le taux d’absorption apparent similaire du BPS-d8 et BPSG-d8 après une exposition par voie orale suggère que les formes libres et conjuguées du BPS atteignent la circulation sanguine systémique à peu près dans le même intervalle de temps. Ceci indique un effet de premier passage hépatique, c’est-à-dire une conjugaison du BPS-d8 dans le foie avant d’atteindre la circulation systémique. Néanmoins, malgré l’effet de premier passage, la biodisponibilité du BPS-d8 et donc la forme active non conjuguée du BPS dans le sang est relativement élevée. Celle-ci est en fait largement plus importante que celle du BPA. Le BPS libre s’est aussi avéré avoir a un temps de résidence plasmatique plus long que le BPA. Pour la voie cutanée, les données ont montré que le BPS atteignait rapidement la circulation sanguine systémique et était donc rapidement absorbé par peau. Par contre, son élimination du corps semble être plus lente après exposition cutanée comparativement à son élimination après exposition orale. Par ailleurs, malgré le fait que le BPS serait rapidement absorbé au niveau de la peau, la fraction d’absorption cutanée était très faible par rapport à la fraction d’absorption orale. / The measurement of bisphenol-S (BPS) and its glucurono-conjugate (BPSG) in urine may be used for the biomonitoring of exposure in populations. However, this requires a thorough knowledge of their toxicokinetics. The time courses of BPS and BPSG were assessed in accessible biological matrices of orally and dermally exposed volunteers. Under the approval of the Research Ethics Committee of the University of Montreal, six volunteers were orally exposed to a BPS-d8 deuterated dose of 0.1 mg/kg body weight (bw). One month later, 1 mg/kg bw of BPS-d8 were applied on 40 cm2 of the forearm and then washed 6 h after application. Blood samples were taken prior to dosing and at fixed time periods over 48 h after treatment; complete urine voids were collected pre-exposure and at pre-established intervals over 72 h postdosing. Following oral exposure, the plasma concentration–time courses of BPS-d8 and BPSG-d8 over 48 h evolved in parallel and showed a rapid appearance and elimination. Average peak values (±SD) were reached at 0.7 ± 0.1 and 1.1 ± 0.4 h postdosing and mean (±SD) apparent elimination half-lives (t½) of 7.9 ± 1.1 and 9.3 ± 7.0 h were calculated from the terminal phase of BPS-d8 and BPSG-d8 in plasma, respectively. The fraction of BPS-d8 reaching the systemic circulation unchanged (i.e. bioavailability) was further estimated at 62 ± 5% on average (±SD) and the systemic plasma clearance at 0.57 ± 0.07 L/kg bw/h. Plasma concentration–time courses and urinary excretion rate profiles roughly evolved in parallel for both substances, as expected. The average percent (±SD) of the administered dose recovered in urine as BPS-d8 and BPSG-d8 over the 0–72 h period postdosing was 1.72 ± 1.3 and 54 ± 10%. Following dermal application, plasma levels were under the lower limit of quantification (LLOQ) at most time points. However, peak values were reached between 5 and 8 h depending on individuals, suggesting a slower absorption rate compared to oral exposure. Similarly, limited amounts of BPS-d8 and its conjugate were recovered in urine and peak excretion rates were reached between 5 and 11 h postdosing. The average percent (±SD) of the administered dose recovered in urine as BPS-d8 and BPSG-d8 was about 0.004 ± 0.003 and 0.09 ± 0.07%, respectively. This study provided greater precision on the kinetics of this contaminant in humans and, in particular, evidenced major differences between BPA and BPS kinetics with much higher systemic levels of active BPS than BPA, an observation explained by a higher oral bioavailability of BPS than BPA. These data should also be useful in developing a toxicokinetic model for a better interpretation of biomonitoring data. Overall, this study provided greater precision on the kinetics of this contaminant in humans. These data will be useful in developing a toxicokinetic model for a better interpretation of biomonitoring data. For the oral route of exposure, the apparent similar absorption rate of BPS-d8 and BPSG-d8 after oral exposure suggests that free and conjugated forms of BPS reach the systemic blood circulation at about the same time interval. This indicates a first-pass effect in the liver, i.e. a conjugation of BPS-d8 in the liver before reaching the systemic circulation. Nevertheless, despite the first-pass effect, the bioavailability of BPS-d8 and therefore the proportion of unconjugated active form of BPS reaching the systemic bloodstream is relatively high. It is actually much higher than that of BPA. Free BPS was also found to have a longer plasma residence time than BPA. For the dermal route of exposure, data show that BPS quickly reaches systemic blood circulation and is therefore rapidly absorbed by skin. On the other hand, its elimination from the body appears to be slower after dermal exposure compared to its elimination after oral exposure. Furthermore, despite the fact that BPS is rapidly absorbed through the skin, the dermal absorption fraction was very small compared to the oral absorption fraction.