Avloppsreningsverk utgör en viktig spridningsväg för läkemedelsrester till den akvatiska miljön. Även per- och polyfluorerade alkylsubstanser (PFAS) har påvisats i utgående vatten från avloppsreningsverk. För att minska utsläpp av dessa krävs ett kompletterande reningssteg. Syftet med denna studie var att utvärdera utökad rening av avloppsvatten med granulerat aktivt kol (GAK) och anjonbytare (AIX, Anion exchange resin). Underlag för utvärdering utgjordes av resultat från pågående pilotstudie vid Kungsängsverket i Uppsala, vilken består av kolonnförsök samt pilotförsök i större skala. I kolonnförsöken testas kombinationen GAK (Cyclecarb 401 eller Filtrasorb 400) i fixerade bäddar, följt av AIX (Purolite 694E) i fixerade samt fluidiserade bäddar i olika driftlinjer. Kontakttiden (EBCT, Empty Bed Contact Time) var cirka 15 minuter för GAK respektive 5 minuter för AIX. I pilotförsöken inkluderas även tvåstegsdrift av GAK med EBCT på cirka 14 minuter per filter. Vid slutet av denna studie hade cirka 36 000 till 37 000 bäddvolymer (BV) behandlats med GAK, respektive 98 000 till 116 000 BV med AIX i kolonnförsöken. I pilotförsöken hade cirka 5 000 till 10 000 BV behandlats med GAK samt cirka 8 000 till 31 000 BV med AIX. Reningseffektivitet utvärderades avseende avskiljning av diklofenak, oxazepam, metoprolol, citalopram samt PFOS eftersom dessa i tidigare studie pekats ut som mest utmanande för mottagande vattenmiljö. En högre avskiljning av oxazepam, metoprolol och citalopram uppnåddes med GAK än med AIX, där Cyclecarb 401 uppvisat högst reduktion. För diklofenak och PFOS uppnåddes en högre avskiljning med kombinationen GAK följt av AIX än med enbart GAK. Driftkostnad och klimatpåverkan utvärderades för samtliga adsorbenter samt för specifika scenarion vid Kungsängsverket. Scenarierna inkluderar olika reningsmål för avancerad rening med singel- respektive tvåstegsdrift av GAK samt GAK följt av AIX. Reningsmålen avser en 80 procentig genomsnittlig reduktion över tid av diklofenak, oxazepam, PFOS eller en kombination av dessa. Vid ekvivalent dos av adsorbenterna resulterade Cyclecarb 401 i den lägsta driftkostnaden och klimatpåverkan. Lägst driftkostnad för samtliga reningsmål erhölls med tvåstegsdrift av GAK. För avskiljning av PFOS eller PFOS och diklofenak erhölls lägst klimatpåverkan med kombinationen GAK följt av AIX. För resterande reningsmål erhölls lägst klimatpåverkan med tvåstegsdrift av GAK. I tillägg utfördes en regressionsanalys för att undersöka om enkla mätningar av löst organiskt kol (DOC) eller ultraviolett absorbans (UVA) kan användas som uppföljningsmetod för reningseffektiviteten. Ingen korrelation kunde dock fastställas mellan skillnaden i ingående och utgående koncentration eller absorbans av DOC, UVA och diklofenak, oxazepam eller PFOS. / Wastewater treatment plants are an important source for the spread of pharmaceuticals to the aquatic environment. Per- and polyfluorinated alkyl substances (PFASs) have also been detected in outgoing wastewater. To reduce emissions of these micropollutants, an advanced treatment process is required.  This study aimed to evaluate advanced treatment with granular activated carbon (GAC) and anion exchange resin (AIX), using results from an ongoing pilot study at the wastewater treatment plant Kungsängsverket in Uppsala, Sweden. The pilot study consists of column tests and pilot tests in larger scale. The column tests consist of the combination of GAC (Cyclecarb 401 or Filtrasorb 400) in fixed beds, followed by AIX (Purolite 694E) in fixed or fluidized beds in different operating lines. Contact time (EBCT, Empty Bed Contact Time) was 15 minutes for GAC and 5 minutes for AIX. The pilot tests include two-stage operation of GAC with EBCT of 14 minutes per filter. At the end of this study, in the column tests, approximately 36 000 bed volumes (BV) had been treated with GAC and 98 000 to 116 000 BV with AIX. In the pilot tests, 5 000 to 10 000 BV had been treated with GAC and 8 000 to 31 000 BV with AIX. Treatment efficiency was evaluated for diclofenac, oxazepam, metoprolol, citalopram and PFOS, since these were identified as prioritized substances in a previous study. A higher reduction of oxazepam, metoprolol and citalopram were obtained using GAC compared to AIX, where Cyclecarb 401 showed the highest reduction. For diclofenac and PFOS, a higher reduction was achieved for the combination of GAC followed by AIX compared to GAC alone.  Operating cost and climate impact were evaluated for the adsorbents as well as for specific scenarios at Kungsängsverket, that includes different treatment goals for single stage and two-stage operation of GAC, and GAC followed by AIX. Treatment goals consists of an 80 percent average reduction over time of diclofenac, oxazepam, PFOS, or a combination of these. For an equivalent dose of adsorbent, the lowest operating cost and climate impact was obtained with Cyclecarb 401. The lowest operating cost for all the treatment goals was obtained with two-stage operation of GAC. For reduction of PFOS or PFOS and diclofenac, the lowest climate impact was obtained with the combination of GAC followed by AIX. For the remaining treatment goals, the lowest climate impact was obtained with two-stage operation of GAC.   In addition, a regression analysis was preformed to evaluate whether measurements of dissolved organic carbon (DOC) or ultraviolet absorbance (UVA) could serve as a prediction method for the treatment efficiency of organic micropollutants. However, the regression analysis showed no correlation between the reduction of DOC, UVA, and diclofenac, oxazepam or PFOS.

Perfluoroalkyl acids (PFAAs) are man-made chemicals which have been observed in the global environment, even in locations far away from where they are emitted. These persistent substances are taken up in humans and biota and may have toxic effects. Knowledge about how PFAAs are dispersed in the environment is needed to discern strategies to manage their sources and to evaluate the efficacy of adopted legislation. This thesis aimed to increase our understanding of the sources of PFAAs to the atmosphere and how PFAAs are transported in air. The results of Paper I demonstrated that gaseous perfluorooctanoic acid (PFOA) sorbs to typical glass fibre filters (GFFs) used in high-volume air sampling of PFAAs. As a consequence, the fraction of gaseous PFOA present in sampled air is underestimated, while the fraction of PFOA associated with aerosols is overestimated. Replacing GFFs with filters deactivated through silanisation and siliconisation did not eliminate this sampling artefact and is therefore not recommended as a means to determine the gas-particle partitioning of PFAAs. In Paper II, monitoring of the mass of PFOA transferred from water solutions of pH 0.2-5.5 demonstrated that the acid dissociation constant of linear PFOA and the four most ubiquitous branched PFOA isomers is around or below 1. Furthermore, the results demonstrated that the presence of counter ions and organic matter in water retarded, rather than enhanced, the volatilisation of PFOA. Therefore, volatilisation of all isomers of PFOA from environmental waters is expected to be negligible. To further study the transfer of PFAAs from environmental waters to air, Paper III simulated the process of sea spray generation in the laboratory. Strong enrichment of PFAAs was observed from bulk water to the surface microlayer and to aerosols. The enrichment increased with PFAA chain length, indicating that this process is of greater importance for more surface active substances. The highest enrichment was observed in aerosols &lt; 1.6 µm, which can travel over long distances if not rained out. Based on the measured aerosol enrichment factors we estimated that approximately 70 metric tonnes of PFAAs are aerosolised from the global oceans yearly and that 3% of this mass is deposited in terrestrial environments. Paper IV reported the occurrence of branched PFOA isomers in deposition sampled in five geographical locations. The presence of these isomers demonstrated that atmospheric transformation of fluorotelomer alcohols is not the only ongoing source of PFAAs to air. We hypothesised that, additionally, both sea spray aerosols and direct emissions from manufacturing sources contributed to the contamination of the precipitation on different spatial scales. Although further research is required to determine the relative importance of different sources to the atmosphere locally and globally, this thesis has substantially advanced the state-of-the-science by i) demonstrating the significance of an air sampling artefact discussed as an uncertainty in the scientific literature over the past decade, ii) definitively ruling out volatilisation from environmental waters as a source of PFOA to air, iii) demonstrating transfer of PFAAs from seawater to air via sea spray aerosols and thus quantifying the environmental importance of this process, and iv) ultimately demonstrating that several types of sources of PFAAs impact the global atmosphere and thus PFAA contamination patterns in precipitation. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript.</p>

During the last two decades, the applications of fluorocarbon based chemicals to provide soil resistant or soil release properties for automotive interior and upholstery have increased tremendously. But, recent studies showed that the soil resistant treatment based on fluorochemicals has detrimental effects on the environment as well as on humans due to the presence of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) content. PFOS and PFOA are toxic, bio accumulative and bio persistent fluoro-organic compounds. This project focus on PFOS and PFOA-free soil resistant chemicals and their application on interior textiles used for automotive. Literature study was done by keeping in mind all the aspects regarding soil and nature of soils, soil resistant mechanism, PFOA and PFOS-free soil resistant chemicals, chemistry of the chemicals, area of the application and the method of application. Experimental application of PFOA and PFOS-free soil resistant chemicals by using different concentrations on 100% Polyester dyed and unfinished fabric was performed with Pad-Dry-Cure method. Experimental application was carried out to evaluate the soil resistant treated samples for soil resistant, clean ability and colour change results. At the end, the comparison of the results of three mentioned evaluations gave us the best possible alternatives. / Program: Magisterutbildning i textilteknologi

Background: Prenatal exposure to perfluoroalkyl substances (PFAS) has been associated with lower birth weight in epidemiologic studies. This association could be attributable to glomerular filtration rate (GFR), which is related to PFAS concentration and birth weight. Objectives: We used a physiologically based pharmacokinetic (PBPK) model of pregnancy to assess how much of the PFAS–birth weight association observed in epidemiologic studies might be attributable to GFR. Methods: We modified a PBPK model to reflect the association of GFR with birth weight (estimated from three studies of GFR and birth weight) and used it to simulate PFAS concentrations in maternal and cord plasma. The model was run 250,000 times, with variation in parameters, to simulate a population. Simulated data were analyzed to evaluate the association between PFAS levels and birth weight due to GFR. We compared simulated estimates with those from a meta-analysis of epidemiologic data. Results: The reduction in birth weight for each 1-ng/mL increase in simulated cord plasma for perfluorooctane sulfonate (PFOS) was 2.72 g (95% CI: –3.40, –2.04), and for perfluorooctanoic acid (PFOA) was 7.13 g (95% CI: –8.46, –5.80); results based on maternal plasma at term were similar. Results were sensitive to variations in PFAS level distributions and the strength of the GFR–birth weight association. In comparison, our meta-analysis of epidemiologic studies suggested that each 1-ng/mL increase in prenatal PFOS and PFOA levels was associated with 5.00 g (95% CI: –21.66, –7.78) and 14.72 g (95% CI: –8.92, –1.09) reductions in birth weight, respectively. Conclusion: Results of our simulations suggest that a substantial proportion of the association between prenatal PFAS and birth weight may be attributable to confounding by GFR and that confounding by GFR may be more important in studies with sample collection later in pregnancy.

Per- and polyfluoroalkyl substances are a large group of global environmental contaminants. They can be divided into two sub-groups, 1) perfluoroalkyl acids (PFAAs) and 2) so called precursors, i.e. compounds that can potentially be transformed to form PFAAs. PFAAs are today ubiquitous in wildlife and humans. Food and drinking water are assumed to be the dominant human exposure pathways for PFAAs. The main aim of this doctoral thesis was to develop highly sensitive and fully validated analytical methods for the determination of a range of PFAAs and selected precursors in dietary samples. The methods were based on liquid chromatography coupled to mass spectrometry. Samples were extracted by solvent extraction followed by a cleanup step employing solid phase extraction. The cleanup step could at the same time be used as a fractionation of ionic PFAAs and neutral precursors. Paper I and II describe the development of methods for simultaneous analysis of three groups of PFAAs including perfluoroalkyl phosphonic acids (PFPAs) in drinking water and food. Methyl piperidine was used as ion pairing agent, leading to highly sensitive analysis of PFPAs. A first screening of tap water samples and different food items revealed that human dietary exposure to PFPAs in Europe is currently not of concern. A novel method for simultaneous analysis of perfluoroalkyl carboxylic acids (PFCAs) and polyfluoroalkyl phosphate esters (PAPs) in food and packaging materials is described in paper III. Targeted food samples and their packaging were analyzed. The results showed that PAPs may contribute to human exposure to PFCAs. In paper IV temporal trends (1991-2011) of perfluorooctane sulfonic acid (PFOS) and its precursors in herring were investigated. Rapidly decreasing trends were found for precursors, whereas PFOS did not show a significant change over time. Precursors in fish may have played an important role for human exposure to PFOS in the 1990s but are probably negligible today. / <p>At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript.</p> / PERFOOD project (KBBE-227525)

BAKGRUND: Per- och polyfluorerade alkylsubstanser, PFAS, är ett samlingsnamn för en stor grupp mycket stabila substanser. Vissa PFAS är klassade som persistenta, bioackumulerbara och toxiska (PBT-ämnen) och har en negativ hälsoeffekt på människor och djur. De är vanligt förekommande i exempelvis brandskum och förhöjda halter finns därför ofta i vattensystem som ligger nära brandövningsområden. Perflourooktansyra (PFOS) är idag den enda PFAS som är förbjuden inom EU och är förmodligen den mest toxiska. Tolerabla gränsvärden finns idag endast för två PFAS; PFOS och PFOA. En av de största källorna för humanexponering av PFOS är fiskkonsumtion, medan PFOA inte brukar vara detekterbar i fisk. SYFTE: Syftet med denna studie var att analysera humanexponering av 11 olika PFAS (PFOS, PFOA, PFHxA, PFHxS, PFHpA, PFNA, PFDA, PFDS, PFBS, PFUnDA och PFOSA) efter konsumtion av abborre (Perca fluviatilis), baserad på analysdata från Stockholms stads miljögiftsövervakning. Då fokus i arbetet framförallt ligger på PFOS så har uppskattat PFOS-intag via denna exponeringsväg jämförts med tillgängliga toxikologiska referensvärden. Likaså syftar arbetet att undersöka hur PFOS- exponeringen via konsumtion av sötvattenfisk förhåller sig till bakgrundsexponering av PFOS i normalbefolkningen. METOD: PFOS-exponeringen via konsumtion av sötvattenfisk beräkandes för tvånivåer av fiskkonsumenter; ”mest sannolik exponeringsnivå” (MSE, där man äteregenfångad sötvattenfisk max 6 ggr per år), och ”hög exponeringssnivå” (HE, där manäter egenfångad sötvattenfisk 1 ggr/vecka). En vidare uppdelning gjordes på”normalkonsumenter” (person som äter normalstora portioner och har en medelvikt) och ”storkonsumenter” (person med låg vikt som äter stora portioner). Beräkningarna grundar sig på tre års analysdata (2015-2017) på abborre från 14 olika vattensystem kring Stockholm stad, vilka kan betraktas som representativa fiskevatten i en urban miljö, utan känd PFOS-påverkan från punktkälla. PFOS-analyser i fisk användes tillsammans med data från litteraturen över fiskkonsumtion och kroppsvikt. Litteraturdata användes även för att beräkna exponeringen i normalbefolkningen viaandra livsmedel och dricksvatten. Även här gjordes beräkningarna för ”mest sannolik exponering” (normalkonsumtion av dricksvatten och normalexponering av PFOS via övriga livsmedel) och ”hög exponering” (storkonsumtion av dricksvatten och högexponering via övriga livsmedel). Därefter jämfördes resultatet med tolerabla dagliga intag (TDI) och PFOS-exponeringen via fiskkonsumtion relaterades till det PFOS-intag som normalbefolkningen blir utsatt för via konsumtion av dricksvatten och andra livsmedel. RESULTAT: I de analyserade proverna av abborrmuskel stod PFOS för ca 90% av PFAS-innehållet, PFOS är den förening som exponeringsberäkningarna gjorts för. Bakgrundsexponeringen för PFOS i normalbefolkningen, via konsumtion av dricksvatten och andra livsmedel (även köpt fisk), beräknades till ca 0,5 ng/kg/dag (vuxna) och 0,7 ng/kg/dag (barn) för den mest sannolika exponeringsnivån (MSE). För den högre exponeringsnivån (HE) beräknades intaget till ca 1,7 ng/kg/dag för både vuxna och barn – alltså väl under EFSAs rådande TDI-värde på 150 ng/kg/dag. Vid jämförelse med dessa bakgrundsnivåer visade sig följande för de 4 exponeringsnivåer som karakteriserats vid konsumtion av egenfångad insjöfisk: MSE – normalkonsument: I denna grupp var PFOS-exponeringen via konsumtionen av egenfångad sötvattenfisk omkring 0,5 ng/kg/dag (vuxna) och 1,1 ng/kg/dag (barn), innebärandes att redan individer som konsumerar egenfångad fisk 6 ggr/år dubblerar sin PFOS-exponering. Det totala intaget ligger dock långt ifrån rådande TDI-värde. MSE – storkonsument: För vuxna och barn beräknades PFOS-exponeringen via sötvattenfisk till ca 1 respektive 2 ng/kg/dag. HE – normalkonsument: För kvinnor blev PFOS-exponeringen 17 ng/kg/dag och för män 18 ng/kg/dag medan resultatet för barn var 37 ng/kg/dag. HE – storkonsument: PFOS-exponeringen från insjöfiskkonsumtion, i detta ”worst-case-scenario”, var 27 och 33 ng/kg/dag för kvinnor respektive män och 69 ng/kg/dag för barn. Hos denna grupp blev exponeringen runt 15 gånger högre än i normalbefolkningens hos vuxna och 40 gånger hos barn. DISKUSSION: Att PFOS stod för den största delen PFAS stämmer väl med förväntat resultat. Studien visar att normal- och storkonsumtion, inom ”den mest sannolika exponeringsnivån”, av sötvattenfisk från de vattensystem i närheten av Stockholm stadsom omfattats av studien, inte utgör någon hälsofara enligt de TDI som gäller idag även om det ger en procentuellt sett stor ökning av PFOS-intaget relativt vad som normalt är att förvänta via intag av livsmedel (även dricksvatten inräknat). Storkonsumenter inomkategorin ”hög exponeringsnivå” utgör ett worst case-scenario, där barn i gruppen kommer upp i ungefär halva TDI. Vid eventuell revidering av TDI så finns risk att både normal- och storkonsumenter, inom ”hög exponeringsnivå”, av sötvattenfisk hamnar påPFOS-intag runt eller över TDI. / BACKGROUND: Per- and polyfluorinated alkyl substances (PFAS) is a group of very stable molecules. Some PFAS are classed as persistant, bioaccumulative and toxic (PBT-substances) with negative impacts on humans and animals. PFAS is a common ingredient in fire foam, and elevated levels are consequently often seen in water systems near fire drill areas. Today, perflourooctanoic acid (PFOS) is the only prohibited PFAS within the EU, and probably the most toxic.Tolerable daily intake (TDI) recommenadtions are only available for two PFAS within the EU; PFOS and PFOA. One of the main exposure routes of PFOS in humans are consumption of fish, whilePFOA usually isn’t detectable in fish. OBJECTIVES: The aim of this study was to analyze human exposure of 11 different PFAS (PFOS, PFOA, PFHxA, PFHxS, PFHpA, PFNA, PFDA, PFDS, PFBS, PFUnDA och PFOSA) after consumption of european perch (Perca fluviatilis) collected from water systems in an urban region of Sweden. The main focus substance of the study was PFOS, where different scenarios of PFOS-exposure after consumtion of perch were compared with toxicological reference values (TDIs) and with background exposure from consumtion of other foods and drinking water. METHODS: The PFOS-exposure from consumption of freshwater fish was calculatedfor two levels of consumers; a “most likely exposure level” (MSE, with a consumptionrate of maximum 6 times/year), and a “high exposure level” (HE, with a consumption rate of at least 1 time/week). The groups were further divided into “normal consumers” (who ate normal portions and had normal body weight) and “large consumers” (who atelarge portions and had a low body weight). The caclulations were based on three years of analysis data (2015-2017) on european perch from 14 different water systems around the city of Stockholm, which can be considered as representative fishing waters in an urban environment, without known PFOS point source. The analyzed PFOS concentrations in fish were used in conjunction with literature data on fish consumption and body weight to assess exposure. Data from the litterature were also used to calculate the exposure in the normal population, after consumption of other foods and drinkingwater. Also here a “most likely exposure level” (average consumtion of drinking water and average consumption rates and PFOS concentrations in other foods) and “high exposure level” (large consumer of drinking water and high PFOS exposure from other foods) were calculated. Thereafter, the results were compared with the tolerable daily intake (TDI), and the PFOS-exposure through consumption of perch was compared to the PFOS-intake following consumtion of other foods and drinking water. RESULTS: PFOS accounted for about 90% of the total PFAS in european perch. PFOS is the compound for which the exposure calculations were made.Background exposure by PFOS in the normal population, through consumtion of drinking water and other foods (including commercial fish), was calculated to 0,5 ng/kg/day (adults) and 0,7 ng/kg/day (children) for the most likely exposure level (MSE). För the higher exposure level (HE) the intake was calculated to 1,7 ng/kg/day for both adults and children, which is far below EFSA ́s current TDI of 150 ng/kg/day. When the background levels are related to the 4 exposure levels characterized after consumption of self-caught freshwater fish the results showed that: MSE – normal consumer: The PFOS exposure from consumption of freshwater fish in this group was 0,5 ng/kg/day (adults) and 1,1 ng/kg/day (children), which means that by consuming self-caught fish 6 times/year the PFOS-exposure will be doubled. Even so, the total intake is far below current TDI. MSE – high consumer: PFOS exposure from freshwater fish were 1 ng/kg/day and 2 ng/kg/day for adults and children respectively. HE – normal consumer: The PFOS exposure for women were 17 ng/kg/day and 18 ng/kg/day for men while the result form children were 37 ng/kg/day. HE – high consumer: The PFOS exposure in this “worst case scenario” was 27 and 33ng/kg/day for women and men respectively and 70 ng/kg/day for children. In this group the exposure were about 15 times higher than the background exposure for adults and 40 times higher for children. CONCLUSIONS: That PFOS accounted for the largest part of PFAS in fish is in accordance with previously published studies. Normal and large consumption offreshwater fish within the “MSE”-group, of freshwater fish, from the water systems near the city of Stockholm which are covered in the study, is not a health risk according to the TDI that apply today. However, it gives a percentually large increase in PFOS intake relative to what is normally expected from food intake (including drinkingwater). High consumers in the “HE”-group constitute a worst case scenario, where children in the group reach a PFOS-exposure of about half of TDI. In the event of a possible revision of TDI also normal consumers in the “HE”-group may close in to, or pass, the TDI-limits.

Perfluorerade alkylsyror (PFAS) är en grupp ämnen som de senaste åren har uppmärksammats för dess persistenta, bioackumulerande och toxiska egenskaper för människor och djur. Det är känt att brandövningsplatser där det filmbildande skummet AFFF har använts utgör betydande punktkällor för PFAS. Förutom att förorena marken vid brandövningsplatserna kan PFAS spridas med grundvattnet, vilket har orsakat förorenade dricksvattentäkter på ett flertal platser i Sverige. Hydrogeologiska modeller kan användas för att modellera grundvattnets flöden och medföljande föroreningar. Syftet med examensarbetet är att med en hydrogeologisk modell undersöka föroreningsspridning och transporttider av PFAS-ämnet perfluoroktansulfonat (PFOS) från en brandövningsplats till ytvatten och grundvattentäkter i Bredåkradeltat, väster om Kallinge i Blekinge. Den hydrogeologiska modellen skapades i Visual MODFLOW och transportmodelleringen gjordes med MT3D99 och MODPATH. Modellen kunde reproducera uppmätta grundvattennivåer, med en korrelationskoefficient (R) på 0,98 mellan modellerade och uppmätta nivåer. Med antagandet försumbar adsorption visade modellresultaten att en föroreningsplym med hög PFOS-koncentration (~90.000 ng/l) spreds från brandövningsplatsen till ett våtmarksområde väster om Klintabäcken, och vidare till dalen längs Klintabäcken med lägre koncentrationen (0–4.000 ng/l). Enligt modellen spreds dock inte föroreningen lika långt som uppmätta värden visar. När PFOS väl har nått Klintabäcken bedöms den kunna spridas snabbt med ytvattnet mot grundvattentäkterna, för att sedan infiltrera ned i isälvsmaterialet nära aktiva grundvattentäkter. Transporttiden av PFOS från brandövningsplatsen till Klintabäcken beräknades till sex år för den bäst kalibrerade modellen, vilket betyder att grundvattentäkterna kan ha varit förorenade sedan slutet av 1980-talet eller början av 1990-talet. Beräkningar av masstransport indikerar att runt 3,5 kg PFOS flödar genom Klintabäcken varje år, och att det mesta av den mängden kommer från området vid brandövningsplatsen. Trots förenklingar av Bredåkradeltats komplexa geologi och svårigheter att nå konvergens i modellen bedöms den kunna reproducera hydrogeologiska egenskaper inom deltat, samt föroreningsplymens spridning från brandövningsplatsen till Klintabäcken.

Les composés perfluorés (PFC) de formule chimique générale CF3-(CF2)n-SO3- ( sulfonates) ou CF3-(CF2)n-1-CO2- (acides) sont des polluants organiques émergents, dont la persistance, la bioaccumulation et la toxicité sont maintenant considérées préoccupantes au plan sanitaire et environnemental. L'objectif de notre recherche a été de mettre en évidence les effets cancérogènes in vitro et le mécanisme d'action impliqué lors de l'exposition pendant 7 jours de cellules embryonnaires de hamster Syrien (SHE) aux principaux représentants perfluorés, le sulfonate de perfluorooctane (PFOS), le perfluorooctanoate (PFOA), et à leur substitut, le sulfonate de perfluorobutane (PFBS). Le test de transformation cellulaire dans sa version standard ou selon un protocole de type initiation-promotion a permis de détecter les substances cancérogènes de profil initiateur ou promoteur de tumeur. La génotoxicité des PFCs a été explorée par le test Comet en conditions alcalines. PFOS a présenté un profil cancérogène non génotoxique de type initiateur aux concentrations de 0,37 et 3,7 µM (p<=0,01), coïncidant avec les concentrations sériques des travailleurs exposés au PFOS. L'activation des gènes PPARs a été observée après 7 jours d'exposition au PFOS, avec une induction plus importante et plus précoce (dès 24 heures d'exposition) du gène ppar-bêta/gamma aux concentrations transformantes (p<=0,05). PFOA appliqué seul n'induit pas la transformation néoplasique des cellules SHE. Par contre, il induit la transformation des cellules présensibilisées par un initiateur. Il agit selon un profil cancérogène non génotoxique de type promoteur de tumeur aux concentrations de 3,7 x 10-4 à 37 µM. Ces concentrations coïncident avec les concentrations sériques mesurées dans les populations professionnellement et non professionnellement exposées. PFBS ne s'est révélé ni initiateur, ni promoteur de tumeur. La mise en cause de ces PFCs dans l'augmentation des cancers de la vessie (pour le PFOS) et celui de la prostate (pour le PFOA) chez les travailleurs exposés ne peut être exclue / Perfluorinated compounds (PFCs) is a collective name for fluorinated surfactants and polymers with the general structure CF3-(CF2)n-SO3- (sulfonates) or CF3-(CF2)n-1-CO2- .(acids). This group is characterized by a high persistence, bioaccumulation and long term toxicity which are rising environmental and public health concerns. In the present work, we analyzed the in vitro carcinogenic potential of the two major PFCs, perfluorooctane sulfonate (PFOS), and perfluorooctanoic acid (PFOA), and their substitute, perfluorobutane sulfonate (PFBS). Cell transformation assays were carried out on Syrian hamster embryo (SHE) cells in a 7 day-treatment using the standard and the initiation-promotion protocols. Genotoxicity was tested using the comet assay. PFOS was not genotoxic on SHE cells, but it induced cell transformation at non cytotoxic concentrations 0,37 and 3,7 µM (p<=0,01). These concentrations coincided with serum PFOS concentrations measured in occupationally exposed workers. An increased expression of PPARs was registered after 7 days. The ppar-beta/gamma mRNA appeared to increase rapidly (24 hours after PFOS treatment) at concentrations closely related to cell transformation (p<=0,05). PFOA was inactive alone, but induced cell transformation of SHE cells pre-initiated with benzo(a)pyrene (BaP). Therefore PFOA was shown to act as a tumor promoter and a non genotoxic carcinogen at a large range of concentrations (3,7 x 10-4 à 37 µM). This range of concentrations covered seric concentrations in non-occupationally exposed and occupationally exposed populations. PFBS was negative alone and on BaP-pretreated SHE cells. For this reason, its use as a substitute for PFOS appears to be justified. To conclude, the cell transforming potenty of PFOS and PFOA denotes in vitro carcinogenic potential. Consequently, the hypothesis of their implication in human cancer recorded in occupationally exposed populations cannot be ruled out

Background In some cross-sectional epidemiologic studies the shape of the association between serum concentrations of perfluoroalkyl acids (PFAAs) and lipids suggests departures from linearity. Objectives We used statistical approaches allowing for non-linearity to determine associations of prenatal exposures of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) with lipid concentrations. Methods PFAAs were measured in serum from pregnant women collected in 1991–1992 at enrollment in the Avon Longitudinal Study of Parents and Children and lipids in serum from their daughters at ages 7 (n = 111) and 15 (n = 88). The associations of PFAAs with lipids were first explored by cubic splines, followed by piecewise linear regressions by tertiles to obtain regression coefficients (β) and their 95% confidence limits (95% CL) (in mg/dL per 1 ng/mL). Results At age 7, total cholesterol was positively associated with prenatal PFOA concentrations in the lower tertile (β = 15.01; 95% CL = 2.34, 27.69) but not with PFOA concentrations in the middle (β = − 3.63; 95% CL = − 17.43, 10.16) and upper (β = − 1.58; 95% CL = − 4.58, 1.42) tertiles. At age 15, a similar pattern was noted as well. Positive associations between LDL-C and prenatal PFOA concentration in the lower tertile were observed in daughters at ages 7 (β = 14.91; 95% CL = 3.53, 28.12) and 15 (β = 13.93; 95% CL = 0.60, 27.26). LDL-C was not associated with PFOA concentrations in the middle or upper tertile at any age. Neither HDL-C nor triglycerides was associated with prenatal PFOA exposure. Non-linear patterns of association of total cholesterol and LDL-C with prenatal PFOS were less consistently noted. Conclusion Exposure to low levels of PFOA during prenatal development may alter lipid metabolism later in life. Given the small sample size further replication of the association in large independent cohorts is important.

Perfluoroalkyl compounds (PFCs) are a group of chemical surfactants most notably used in non-stick and stain-resistance applications. Due to their wide-spread use and inherent resistance to degradation, several PFCs have become persistent environmental contaminants. Despite the high concentrations of PFCs reported in wild birds and their eggs, very little is known about the toxicological effects they have on avian species. This thesis investigates the developmental toxicity of PFCs in an avian model species: the domestic chicken (Gallus gallus domesticus). Egg injection experiments were performed to assess the in ovo toxicity of perfluorooctane sulfonate (technical grade, T-PFOS), perfluorooctanoic acid (PFOA), perfluorodecane sulfonate (PFDS) and perfluoroundecanoic acid (PFUdA). Real-time RT-PCR was then used to measure the transcription of candidate biomarker genes in the liver tissue of day 20 embryos. Candidate genes were selected based on their responsiveness to PFC exposure in previously conducted in vitro screening assays. In ovo exposure to PFOS resulted in a dose-dependent decrease in embryo pipping success (a measure of hatching success) with an LD50 of 93 μg/g (3.54 μg/g-672,910 μg/g, 95% confidence interval), however the expression of peroxisome proliferator-activated receptor alpha (PPARα)-regulated genes was not affected in liver tissue as hypothesized. PFOA, PFDS and PFUdA had no effect on the pipping success of chicken embryos. The expression of cytochrome P450 1A4 (CYP1A4) and liver fatty acid binding protein (L-FABP) mRNA increased in embryo liver tissue following in ovo exposure to PFUdA but was only statistically significant at 10 μg/g, which is several orders of magnitude higher than concentrations reported in wild bird eggs. The isomer-specific accumulation of PFOS in chicken embryo livers was also investigated using an in-port derivatization gas-chromatography/mass spectrometry (GC-MS) method. Prior to incubation, chicken eggs were injected with T-PFOS, composed of 63% linear isomer (L-PFOS) and 37.3% branched isomers. The isomer profiles in day-20 embryo liver tissue showed up to 20% enrichment in the proportion of L-PFOS, compared to T-PFOS, with a corresponding decrease in the proportion of branched isomers. This enrichment was inversely proportional to dose. Finally, the transcriptional profiles of cultured chicken embryonic hepatocytes (CEH) exposed to either T-PFOS or L-PFOS were compared using Agilent 4x44k Chicken (V2) Gene Expression microarrays. At equal concentrations (10 μM), T-PFOS altered the expression of significantly more genes (340 genes, >1.5 fold change, false discovery rate adjusted p<0.05) compared to L-PFOS (130 genes). Functional analysis showed that L-PFOS and T-PFOS affected genes involved in lipid metabolism, cellular growth and proliferation, and cell-cell signaling. Pathway and interactome analysis suggested that gene expression may be affected through RXR, oxidative stress response, TP53 signaling, MYC signaling, Wnt/β-catenin signaling and PPARγ and SREBP receptors. In all functional categories and pathways examined, T-PFOS had a more pronounced disruptive effect on transctional regulation than L-PFOS. In summary, egg injection experiments showed that T-PFOS (but not linear PFOA, PFDS or PFUdA) may affect the hatching success of the chicken at environmentally relevant concentrations. It was also demonstrated that the accumulation of PFOS in embryonic liver is isomer specific, and leads to an enrichment of L-PFOS. The increased transcriptional disruption caused by T-PFOS in cultured hepatocytes over L-PFOS suggests that the branched isomers may be largely responsible for the toxicological effects of PFOS. Combined, the results from this thesis demonstrate the importance of considering PFOS isomer burdens during risk assessment. In addition, gene expression analysis identified several candidate mechanisms for PFOS toxicity.