No description available.

Di-(2-ethylhexyl)-phthalate (DEHP), an ubiquitous environmental contaminant, has been shown to cause adverse effects on glucose homeostasis and insulin sensitivity in epidemiological studies, but the underlying mechanisms are still unknown. We therefore tested the hypothesis that chronic DEHP exposure causes impaired insulin sensitivity, affects body weight, adipose tissue (AT) function and circulating metabolic parameters of obesity resistant 129S6 mice in vivo. An obesity-resistant mouse model was chosen to reduce a potential obesity bias of DEHP effects on metabolic parameters and AT function. The metabolic effects of 10-weeks exposure to DEHP were tested by insulin tolerance tests and quantitative assessment of 183 metabolites in mice. Furthermore, 3T3-L1 cells were cultured with DEHP for two days, differentiated into mature adipocytes in which the effects on insulin stimulated glucose and palmitate uptake, lipid content as well as on mRNA/protein expression of key adipocyte genes were investigated.We observed in female mice that DEHP treatment causes enhanced weight gain, fat mass, impaired insulin tolerance, changes in circulating adiponectin and adipose tissue Pparg, adiponectin and estrogen expression. Serum metabolomics indicated a general increase in phospholipid and carnitine concentrations. In vitro, DEHP treatment increases the proliferation rate and alters glucose uptake in adipocytes. Taken together, DEHP has significant effects on adipose tissue (AT) function and alters specific serum metabolites. Although, DEHP treatment led to significantly impaired insulin tolerance, it did not affect glucose tolerance, HOMA-IR, fasting glucose, insulin or triglyceride serum concentrations. This may suggest that DEHP treatment does not cause impaired glucose metabolism at the whole body level.

Les phtalates (PAEs) sont un groupe de contaminants organiques émergents qui sont devenus une préoccupation majeure en raison de leur omniprésence dans le milieu marin et de leurs effets perturbateurs sur le système endocrinien. Cependant, leur répartition en Méditerranée est assez mal connue, principalement en raison des difficultés analytiques et du risque élevé de contamination des échantillons lors du processus analytique. En outre, les débris de plastique en milieu marin contiennent des additifs comme les PAEs, qui sont ajoutés lors de l’étape de fabrication du plastique. Dans la première partie de cette thèse, une méthode analytique a été optimisée et validée pour la détermination de 8 PAEs à l'état de traces en milieu marin. Brièvement, 1L d'échantillon filtré est passé à travers des cartouches de verre contenant 200 mg d'Oasis HLB, puis élué à l’aide de 6mL d'acétate d'éthyle. Notre méthode donne des rendements d’extraction compris entre 95 et 115 % et des blancs acceptables. Dans un second temps, un suivi annuel de la contamination de la Baie de Marseille a été effectué de décembre 2013 à novembre 2014. Les résultats ont montré la présence de 7 PAEs, avec des concentrations totales variant de 130 à 1330 ng L-1. Dans la dernière partie de cette thèse, deux échantillons de plastique communs (sac de poubelle et gaine de câble électrique) ont été incubés dans de l'eau de mer naturelle dans des conditions contrôlées de laboratoire, de manière à évaluer la migration de PAEs depuis ces matériaux en fonction de différentes conditions environnementales comme la température, la présence de lumière, ou encore la présence de bactéries. / Phthalic Acid Esters (PAEs) are a group of emerging organic contaminants that have become a serious issue because of their ubiquitous presence on the marine environment worldwide and for the endocrine disrupting effects in animals and humans. However, little is known about their distribution in the Ocean, mainly because of analytical difficulties and the high possibility of ambient sample contamination. Plastic debris in marine environment includes resin pellets, macro- and microplastic fragments, and contains additives such as PAEs that might be released in the aquatic environment in unknown proportion. In our work, we improved an analytical method for the determination of 8 PAEs, at trace levels in marine and fresh waters. In the first part of the thesis, the method was validated for different seawater salinities and wastewater treatment plant outlet. By passing 1 L of sample through glass cartridges packed with 200 mg of Oasis HLB and eluted with 6 mL of ethyl acetate, the recoveries of 8 PAEs ranged from 95 to 115 % with acceptable blank values (below 0.4-4.0 % of the masses measured in different seawater samples). In a second part, PAE distribution in the Marseille Bay has been evaluated though a one-year monitoring from December 2013 to November 2014. The results showed the occurrence of six PAEs with total concentrations ranging from 130 to 1330 ng L-1. In the last part of this thesis, two common plastic samples as trash plastic bags and insulation layer of electric cables were incubated in natural seawater in laboratory conditions and studied for the release of PAE. Release ws observed for the different PAEs with kinetics varying according to the plastic type.

The need of understanding transport processes of contaminants in groundwater has grownalong with the discovering of contamination of soil and groundwater due to industrialization.Mobility of an organic contaminant in the soil is affected by its partitioning to dissolvedorganic carbon, DOC. Partitioning of hydrophobic organic contaminants, HOCs, to DOC isdescribed by the contaminant’s KDOC value. The effects of DOC on transport processes oforganic contaminants with groundwater are still relatively unexplored even though somereviews have been carried out in this particular field of research. The aim of this thesis workwas to investigate transport processes for the PAH phenanthrene and the phthalate Di(2-ethylhexyl) phthalate, DEHP, with DOC by constructing a transport model with the computerprogram FEFLOW 6.1. The thesis work was performed as part of an ongoing Research &Development project investigating alternative remediation techniques at Domsjö industrialsite, located 2 km south of Örnsköldsvik. Generally, the groundwater at the site was characterized by low phenanthrene and DEHPcontent together with high DOC content. In the sampling points with highest reportedcontaminant concentration also DOC was present in highest concentrations. During theperformed literature study it was found that tabulated KDOC values for phenanthrene wasavailable but not for DEHP, which had to be calculated based on available KOC and KOWvalues. Five different modeling scenarios were developed: 1. Transport of phenanthrene with KDOC minimum value. 2. Transport of phenanthrene with KDOC maximum value. 3. Transport of phenanthrene with KDOC median value. 4. Transport of DEHP with KDOC calculated with KOC. 5. Transport of DEHP with KDOC calculated with KOW. Calculations of contaminant concentration in groundwater were made with an equation thatrequires both site and contaminant specific constants. These constants had to be estimatedduring this thesis work, which resulted in insecurities possibly affecting the model results.However, the minimum and the median value of KDOC showed best modeled phenanthreneconcentration after six years compared to measured values. Best result of modeledconcentrations of DEHP was obtained with KDOC calculated with KOC. Correlation analysis ofDOC and contaminants showed a significant correlation between DOC and phenanthrene at99% confidence level, and between DOC and DEHP at 90% confidence level. / I takt med ökad kännedom om industriellt förorenade områden har det också blivitbetydelsefullt att känna till de processer som påverkar transport av föroreningar medgrundvattnet. Rörligheten av en hydrofobisk organisk förorening, HOC, påverkas av dessfördelning till löst organiskt kol, DOC, och beskrivs med fördelningskoefficienten KDOC.Effekterna av DOC på föroreningstransporten är relativt okända trots att forskning harbedrivits inom området. Syftet med examensarbetet var att undersöka spridning av fenantren(ämnesklass PAH) och Di(2-etylhexyl)ftalat med DOC genom att konstruera enföroreningsspridningsmodell i datorprogrammet FEFLOW 6.1. Examensarbetet utfördes somdel i ett pågående Forsknings & Utvecklingsprojekt med syfte att utreda en alternativsaneringsteknik för Domsjö industriområde, 2 km söder om Örnsköldsvik. Generellt sett karaktäriserades grundvattnet på platsen av låg fenantren- och DEHP-halttillsammans med hög DOC-halt. På samma ställen där föroreningarna förekom i högstakoncentration var också DOC-koncentrationen som högst. Vid genomförd litteraturstudieåterfanns tabellerade KDOC-värden endast för fenantren. KDOC för DEHP saknades och fickberäknas med ekvationer baserat på förhållandet mellan KDOC och KOC respektive KOW. Femolika modelleringsscenarier utvecklades: 1. Spridning av fenantren med minsta tillgängliga KDOC-värde. 2. Spridning av fenantren med högsta tillgängliga KDOC-värde. 3. Spridning av fenantren med median KDOC-värde. 4. Spridning av DEHP med KDOC beräknat med KOC. 5. Spridning av DEHP med KDOC beräknat med KOW. Beräkning av föroreningarnas koncentration i grundvattnet gjordes med en ekvation somegentligen kräver både plats- och föroreningsspecifika konstanter. Då detta inte fanns att tillgågjordes uppskattning av värdena vilket resulterar i osäkerheter som kan ha påverkan påmodellerade resultat. De bästa modellerade koncentrationerna av fenantren efter sex årssimulering jämfört med uppmätta koncentrationer uppnåddes med minsta och median-värdeav KDOC. Bästa modellerade koncentrationerna av DEHP gavs av KDOC beräknat med KOC.Korrelationstest med DOC och respektive förorening visade en signifikant korrelation mellanDOC och fenantren vid 99% konfidensnivå, och mellan DOC och DEHP vid 90% konfidensnivå.

A three-compartment model is extended to estimate the fate and transport of DEHP in a realistic residential environment. The model considered eight environmental media (i.e. air, particulate matter with six size fractions, vinyl flooring, carpet, furniture, dust, wall and ceiling). Particle movement (deposition and resuspension), dust removal (vacuuming), indoor cooking, and adsorption/absorption on indoor surfaces are included. The predicted airborne DEHP concentrations at steady state are within 0.1 [microgram]/m³ to 0.6 [microgram]/m³, which are similar to those measured in field studies. After vinyl flooring (the primary source) is removed, it takes 2 years for the indoor airborne DEHP level to reduce 0.01 [microgram]/m³, and the time increases significantly when carpet present. The results indicate that carpets as well as other interior surfaces may be important phthalate sinks and if the only removal mechanism is ventilation, strongly sorbing phthalate may persist for years. Phthalate amount in dust is strongly influenced by the deposition surface. The concentration of DEHP presents 10 times higher in dust on the source (vinyl flooring) than on the sink (furniture), and it takes more than a year for DEHP to reach equilibrium between bulk air and dust. The domestic activity of cooking is then included in the model and it shows that suspended particle concentration has a substantial impact on gas-phase DEHP level indoors, while the influence of ventilation is only to some extent. Three other SVOCs (DMP, BBP and DiDP) are also investigated and their environmental fates show that chemical’s vapour pressure and octanol/air partition coefficient have substantial influences on sorbing mechanisms and the gas phase and airborne concentrations. / text

No description available.

No description available.

Bisphenol A (BPA), the monomer of polycarbonate plastics and epoxy resins, can disrupt intrauterine implantation of fertilized ova in mice. This effect is also induced by exposure to chronic stress or high doses of diethylhexyl phthalate (DEHP), a plasticizer found in polyvinyl chloride products. I assessed the potential combinatory effects of BPA and stress on blastocyst implantation, uterine morphology, adhesion protein expression, and urinary hormone levels. Subcutaneous injections of BPA administered from gestation days (GDs) 1–4 paired with a stressor (rat exposure across a grid) reduced the number of implantation sites on GD 6 at a dose where neither BPA nor stress had this effect on their own. Uterine luminal area was increased by BPA when paired with stress. BPA reduced epithelial cadherin (e-cadherin), a uterine adhesion protein, independently from the stressor. Urinary estradiol was significantly increased by BPA relative to controls, regardless of stress. In other experiments, effects of concurrent BPA and DEHP administered were assessed. Inseminated female mice were injected with BPA, DEHP, or BPA + DEHP from GDs 1–4. Implantation measured in uteri on GD 6 was disrupted by a combined dose but not by the individual doses. This dose also decreased the amount of e-cadherin and cadherin-11, another adhesion protein expressed by cells, while cadherin-11 was also affected by BPA alone. In further experiments designed to elucidate the interaction of BPA and DEHP, mice were fed 14C-BPA and injected with varied doses of DEHP, then tissues were excised and measured for radioactivity. When given DEHP, males and cycling and peri implantation females showed increased BPA deposition in reproductive tissues and serum. As people are commonly exposed to both DEHP and BPA through consumer products, it is important to determine their interactions and also to understand how dose-response is affected by other factors such as stress. / Thesis / Doctor of Philosophy (PhD)

Di-(2-ethylhexyl)-phthalate (DEHP), an ubiquitous environmental contaminant, has been shown to cause adverse effects on glucose homeostasis and insulin sensitivity in epidemiological studies, but the underlying mechanisms are still unknown. We therefore tested the hypothesis that chronic DEHP exposure causes impaired insulin sensitivity, affects body weight, adipose tissue (AT) function and circulating metabolic parameters of obesity resistant 129S6 mice in vivo. An obesity-resistant mouse model was chosen to reduce a potential obesity bias of DEHP effects on metabolic parameters and AT function. The metabolic effects of 10-weeks exposure to DEHP were tested by insulin tolerance tests and quantitative assessment of 183 metabolites in mice. Furthermore, 3T3-L1 cells were cultured with DEHP for two days, differentiated into mature adipocytes in which the effects on insulin stimulated glucose and palmitate uptake, lipid content as well as on mRNA/protein expression of key adipocyte genes were investigated.We observed in female mice that DEHP treatment causes enhanced weight gain, fat mass, impaired insulin tolerance, changes in circulating adiponectin and adipose tissue Pparg, adiponectin and estrogen expression. Serum metabolomics indicated a general increase in phospholipid and carnitine concentrations. In vitro, DEHP treatment increases the proliferation rate and alters glucose uptake in adipocytes. Taken together, DEHP has significant effects on adipose tissue (AT) function and alters specific serum metabolites. Although, DEHP treatment led to significantly impaired insulin tolerance, it did not affect glucose tolerance, HOMA-IR, fasting glucose, insulin or triglyceride serum concentrations. This may suggest that DEHP treatment does not cause impaired glucose metabolism at the whole body level.

Many products used in our everyday life contain chemicals added to give them specific properties. Flame retardants (FRs) are added to prevent or retard fires in textiles, plastics etc., while plasticizers are supplied to make plastics more flexible. Through their widespread applications chemicals from both groups are emitted and spread in the environment during usage and disposal. For a long time these products were mainly disposed of in landfills, and in many areas they still are. Thus, since some of these chemicals also pose potential environmental risks and health hazards, there is a need to elucidate their fates during exposure to the landfill environmentThe objectives of this thesis were to investigate the leaching and transformation of FRs and plasticizers from products in which they are used under simulated landfill conditions. To assess the importance of changes in these processes as landfills progress through recognised ageing phases (accompanied by large transitions in both physico-chemical and biological conditions) it was desirable to simulate the changes that typically occur in landfills within a short time period, of 1-2 years.. This was achieved using the newly developed intermediate-scale (3 litre) Modular Environmental Test System (METS).The METS were employed in two studies. The first was an investigation of the leaching and degradation of plasticizers from PVC carpet material incubated at different temperatures (20, 37, 55 and 70°C) prevailing in landfills. Plasticizers subjected to this investigation were the phthalates di-2-ethylhexyl phthalate (DEHP) and benzyl-butyl phthalate (BBP), both of which were found to leach from the carpet. The leaching of DEHP and BBP generally increased with increases in the incubation temperature. However, the most rapid leaching of BBP occurred at 37°C, probably due to high microbial activity at this temperature. Both DEHP and BBP were shown to be degraded within the landfill environment and the degradation potential was highest during the methanogenic landfill phase. In the second METS study the leaching of FRs used in both reactive and additive applications (i.e. chemically bonded to and merely blended with the material, respectively) was characterised. The epoxy oligomer tetrabromobishpenol A (TBBPA) and the phosphorus-based Pyrovatex FRs were selected as representatives for the reactive FRs, while the nitrogen-based melamine and phosphorus-based Proban FRs were selected to represent additive classes. During the incubations, which lasted more than two years, the leaching from melamine was shown to be affected by the landfill phase development. The leaching from the Pyrovatex-treated material and the TBBPA epoxy oligomer seemed to result almost entirely from the washout of unreacted manufacturing residuals. This was also probably true for the FR in the Proban-treated material, although it is durable (despite being additively applied) and thus seemed to leach more slowly (manifested as an increase in phosphate levels in the leachate towards the end of the monitoring period).Finally, due to the paucity of knowledge regarding the fate of ether derivatives of TBBPA (which are also used as FRs) an anaerobic degradation assay was performed. The method employed for this assay was a modified, small-scale ISO standard method. In order to evaluate the degradation assay a uniform analytical protocol was developed. The degradation survey showed that losses of TBBPA, TBBPA-dimethyl ether and bisphenol A dimethyl ether occurred, but no losses of the most hydrophobic compound, TBBPA-dibromopropyl ether, were observed. / Många av de varor och produkter vi kommer i kontakt med dagligen innehåller kemikalier, som tillsats för att materialen i produkterna skall få specifika egenskaper. Till dessa sk funktionella kemiska föreningar hör till exempel flamskyddsmedel och mjukgörare. Den förra förhindrar att produkter fattar eld eller minskar omfattningen av brand. Mjukgörare ingår fr a i plaster för att dessa skall bli smidiga och formbara. Eftersom stora mängder av dessa substanser används eller har använts i produkter i samhället har de spridits till många miljöer. Produkterna hamnar ofta på soptipp, då de inte används mer eller är utnötta. Eftersom flera av dessa substanser innebär risk för hälsa och miljö, är det påkallat att utreda hur de beter sig i soptippsmiljön.Syftet med detta avhandlingsarbete är att undersöka eventuell frisättning och omvandling av dessa två typer av funktionella kemikalier i deponimiljö. Sedan tidigare vet man att sådan frisättning kan var starkt kopplad till åldern och därmed utvecklingen av den kemiska och fysiska miljön förändrats fr a genom tillväxten av mikroorganismer i soptippen. För att komma åt att studera frisättningen under de för deponier karakteristiska utvecklingsfaserna utvecklades en metod (Modualr Environmetal Test System; METS) för att simulera faserna över relativt kort tid (ca 1-2 år). I avhandlingen presenteras två studier, där METS utnyttjats: 1) Frisättning av mjukgörare från en PVC-matta i relation till temperaturer, som uppträder i soptippar (20-70oC) samt 2) Läckage av olika flamskyddsmedel i reaktiv respektive additiv användning studerades för olika applikationer. Vid reaktive applikation är flamskyddsmedlet kovalent bundet till polymeren i produktmaterialet, medan det additivt använda flamskyddsmedlet är inblandat i materialet.Två ftalater (di-2-etylhexyl ftalat, DEHP och bensyl-butyl ftalat (BBP), visade sig läcka från mattan, vilket ökade med högre temperature. De frisattes dock som mest vid 37oC, vilket sannolikt beror på den höga mikrobiella aktiviteten vid denna temperatur. Båda ftalterna bröts ned i soptippsmiljön och hastigheten var störst i den metanogena fasen.En epoxyoligomer (tetrabromobishpenol A TBBPA) och Pyrovatex, som bygger på en fosforförening, användes som modeller för reaktiva flamskyddsmedel. Melamin, som klassas som ett kvävebaserat flamskyddsmedel, fick tillsammans med Proban (fosforbaserat) represen-tera de som används additivt. Medan en frisättning av melamin kunde relateras till utvecklingen av deponimiljön simulerad i METS, så verkar den observerade frisättningen av kemikalierna från de reaktivt behandlade Pyrovatexmaterialet och från epoxipolymeren TBBPA förr ha en fysikalisk-kemisk grund oberoende av utvecklingsfaserna i tippmodel-lerna. Flamskyddsmedlen tvättades helt enkelt ut ur de behandlade produkterna. Probanbehandlingen, som motstår förhållandevis många tvättar trots att det används additivt, visade sig läcka långsamt utan en direkt koppling till fasutvecklingen i METS.Kunskaperna om vad som händer med TBBPA:s eterderivat i deponier är i stort sett obefintliga. Flera av dessa derivat används också som flamskyddsmedel. Därför genomfördes en anaerob nedbrytningsstudie av dessa substanser. För att kunna göra denna studie behövdes en omfattande anpassning och utveckling av metodik, vilket resulterade i ett nytt protokoll för analys av dessa ämnen i olika matriser. Studien visade minskning av koncentrationerna av TBBPA, TBBPA-dimetyleter och bisfenol A dimetyl eter, vilket kan tas som ett tecken på att en transformation och/eller nedbrytning skett. Då dessa föreningar kan omvandlas till mer toxiska substanser bör de undersökas vidare.