<p>An extensive use of chemicals in countless consumer products has resulted in human exposure to several persistent organic pollutants (POPs). Sufficient knowledge about their chemical composition properties and environmental faith is required, to be able to proper risk assess and regulate the substances. Significant data gaps exist regarding knowledge of actual exposure to humans and toxicological effect data.</p><p>The objective of this thesis was to add human exposure data of a few POPs from four case studies. The analytes discussed in this thesis are polychlorinated dibenzo-p-dioxins and furans (PCDDs/PCDFs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCDD).</p><p>Three European populations were studied. Milk was analysed from a group of women, who were accidentally exposed to high levels of 2,3,7,8-TetraCDD (TCDD) in Seveso, 1976. Still today, twice as high TCDD levels were recorded in the milk, compared to background concentrations. Serum was analysed from mothers and their infants from The Netherlands. Cord serum contained equal amounts of POPs as in mother’s blood, indicating non-hindered placenta transfer. Serum analysed from Swedish men and women with a high fish intake had elevated PCB and PCB metabolite (OH-PCB) levels. Additionally, butter was collected worldwide and shown to be a suitable matrix for dairy product survey of POPs.</p><p>The exposure levels in the four papers were compared to recently reported exposure levels in Europe. It is indicated in the thesis that the PCDDs/PCDFs and PCBs toxic equivalency (TEQ) levels are of concern, i.e. the ratio between threshold levels for adverse health effects and TEQ exposure levels is lower than requested margin of safety. Average levels of PBDE/HBCDD in the European population are estimated to be of no concern today, but for individuals with intakes at the 95th percentile are the current margins of safety small.</p>

An extensive use of chemicals in countless consumer products has resulted in human exposure to several persistent organic pollutants (POPs). Sufficient knowledge about their chemical composition properties and environmental faith is required, to be able to proper risk assess and regulate the substances. Significant data gaps exist regarding knowledge of actual exposure to humans and toxicological effect data. The objective of this thesis was to add human exposure data of a few POPs from four case studies. The analytes discussed in this thesis are polychlorinated dibenzo-p-dioxins and furans (PCDDs/PCDFs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCDD). Three European populations were studied. Milk was analysed from a group of women, who were accidentally exposed to high levels of 2,3,7,8-TetraCDD (TCDD) in Seveso, 1976. Still today, twice as high TCDD levels were recorded in the milk, compared to background concentrations. Serum was analysed from mothers and their infants from The Netherlands. Cord serum contained equal amounts of POPs as in mother’s blood, indicating non-hindered placenta transfer. Serum analysed from Swedish men and women with a high fish intake had elevated PCB and PCB metabolite (OH-PCB) levels. Additionally, butter was collected worldwide and shown to be a suitable matrix for dairy product survey of POPs. The exposure levels in the four papers were compared to recently reported exposure levels in Europe. It is indicated in the thesis that the PCDDs/PCDFs and PCBs toxic equivalency (TEQ) levels are of concern, i.e. the ratio between threshold levels for adverse health effects and TEQ exposure levels is lower than requested margin of safety. Average levels of PBDE/HBCDD in the European population are estimated to be of no concern today, but for individuals with intakes at the 95th percentile are the current margins of safety small.

Philosophiae Doctor - PhD / Persistent organic pollutants (POPs) are very tenacious wastewater contaminants with negative impact on the ecosystem. The two major sources of POPs are wastewater from textile industries and pharmaceutical industries. They are known for their recalcitrance and circumvention of nearly all the known wastewater treatment procedures. However, the wastewater treatment methods which applied advanced oxidation processes (AOPs) are documented for their successful remediation of POPs. AOPs are a group of water treatment technologies which is centered on the generation of OH radicals for the purpose of oxidizing recalcitrant organic contaminants content of wastewater to their inert end products. Circumvention of the reported demerits of AOPs such as low degradation efficiency, generation of toxic intermediates, massive sludge production, high energy expenditure and operational cost can be done through the application of the combined AOPs in the wastewater treatment procedure. The resultant mineralisation of the POPs content of wastewater is due to the synergistic effect of the OH radicals produced in the combined AOPs. Hydrodynamic cavitation is the application of the pressure variation in a liquid flowing through the venturi or orifice plates. This results in generation, growth, implosion and subsequent production of OH radicals in the liquid matrix. The generated OH radical in the jet loop hydrodynamic cavitation was applied as a form of advanced oxidation process in combination with hydrogen peroxide, iron (II) oxides or the synthesized green nano zero valent iron (gnZVI) for the treatment of simulated textile and pharmaceutical wastewater.

Type 2 diabetes has reached epidemic proportions in adults and youths. Persistent organic pollutants and endocrine-disrupting chemicals (EDCs), such as pesticides, dioxins, and organochlorines, are omnipresent and persist in the environment with potential for human exposure via contaminated air, waterways, soil, and human food supply. EDCs have been correlated with diabetes incidence and risks. Residential proximity to hazardous waste sites (HWS) has been correlated with increased hospital admission rates for diabetes. The study used a sample population (N = 1,724), ages ≥ 12 years from the 2005-2012 Continuous NHANES and HWS data from the National Priorities List of Superfund Sites. The ecosocial theory of disease distribution, and geocoordinates provided theoretical support. Mann-Whitney U test and binary logistic regression analysis were used to investigate the relationship between residence ≤ 1 mile compared with residence >1 mile from a HWS in NHANES surveyed counties of NJ, PA, NY, and CA on the outcome abnormal A1c ≥ 5.7% while controlling the effect of the moderators: abnormal body mass index (BMI), age, sex, and race/ethnicity on the relationship. Participants with a BMI ≥ 28.95 kg/m2 were 1.8 times and persons ≥ 58 years of age were 2.1 times more likely to have an A1c ≥ 5.7%. Also, non-Hispanic Whites residing >1 mile of a HWS had 82.1 % reduced risk of abnormal A1c compared with the same group residing ≤ 1 mile of a HWS. The results forge opportunities for future studies to consider border distance between residence and HWS. In addition, the results may promote positive social change through diabetes risks education, environmental health education, and practices and raise dialogue about social justice and the geographic distribution of hazardous waste sites.

In this study, the Persistent Organic Pollutants (POPs) specifically / 17 Organochlorine Pesticides (OCPs) and 19 Polycyclic Aromatic Hydrocarbons (PAHs) were evaluated in the sediment samples of Balikesir (Ikizcetepeler) Dam Lake. Sixteen sampling points were chosen for determination of concentrations of OCPs and PAHs After ultrasonic bath extraction of the sediment samples GC-MS was used as analytical tool. Extraction efficiencies changes from 63.8 to 87.4% depending on the type of the POPs. Average OCP concentration was found in the range of 3.33-379 &micro / g/kg a, average PAH concentration was found in the range of 3.28-32.9 &micro / g/kg. Pollution maps regarding OCP and PAH distributions were drawn and the correlation between these two pollutant types was investigated. The quality control (QC) and quality assurance tests were applied by the analysis of standard reference materials (SRMs), surrogate standards and analysis replicates.

Les estuaires sont des écosystèmes aquatiques particulièrement soumis au changement global et notamment à la pollution par de nombreux xénobiotiques pouvant présenter un risque écotoxicologique et sanitaire. En toxicologie environnementale et en évaluation des risques la bioaccumulation est un processus fondamental car elle contrôle les doses internes de toxiques potentiels. Or les flux de contamination et de décontamination des organismes dépendent de processus internes (e.g. nutrition, croissance) eux-mêmes dépendant des conditions environnementales (e.g. température, nourriture) qui peuvent être affectées par le changement global.Dans ce contexte, cette thèse se propose de décrire, dans un cadre de modélisation mécaniste, les processus de bioaccumulation de deux familles de polluants organiques persistants (POP) halogénés potentiellement toxiques et bioaccumulables, aux propriétés physico-chimiques contrastées : les polychlorobiphényles (PCB, composés historiques fortement lipophiles) et les substances perfluorées (PFAS, composés émergents amphiphiles). Ce travail se focalise sur l’estuaire de la Gironde dont la fonction de nourricerie est fondamentale pour de nombreuses espèces de poissons marins dont la sole commune (Solea solea), souvent utilisée comme indicatrice de la qualité des nourriceries côtières et estuariennes.Pour permettre de tenir compte des fluctuations des conditions environnementales sur la bioaccumulation, dans la première partie de ce travail, j’ai développé un modèle de toxicocinétique(TK) couplé avec un modèle mécaniste bioénergétique basé sur la théorie DEB (Dynamic Energy Budget). Ce modèle DEB a été paramétré pour la sole commune et calibré pour chaque sexe (package DEB tool). Il permet de prédire les principales évolutions des fonctions physiologiques d’intérêt en bioaccumulation (ingestion, croissance, reproduction...), tout au long du cycle de vie d’un individu, en fonction de conditions environnementales dynamiques. Le modèle TK développé a été complexifié par l’ajout d’un flux d’élimination de contaminants, non considéré dans les précédents modèles DEB-TK.La calibration des paramètres toxicocinétiques (TK) du modèle, pour 4 congénères de PCB, est basée sur une méthode innovante de prise en compte de la variabilité individuelle d’ingestion, appliquée à une expérimentation de contamination de juvéniles de sole via leur nourriture. Ce travail a montré que même en tenant compte de l’ingestion de chaque poisson, l’assimilation efficace de contaminant était très variable et corrélée aux taux de lipides des individus. Dans une seconde partie, ce modèle a été appliqué aux conditions in situ de l’estuaire de la Gironde. Il a permis de mettre en évidence la forte influence de la composition du régime alimentaire sur la variabilité de l’âge à la maturité sexuelle et de la contamination des soles pour les deux familles de contaminant étudiées. La confrontation des prédictions du modèle aux mesures de contaminants dans les juvéniles de sole de l’estuaire a permis de calibrer les paramètres TK du composé majeur de chaque famille dans l’environnement (CB153 et PFOS). Cette calibration a conduit à deux constats dans le cadre de l’évaluation du risque : (1) un manque de connaissances pour extrapoler les calibrations de paramètres TK en conditions contrôlées vers les conditions naturelles ; (2) la différence d’erreur d’évaluation du risque liée à l’utilisation des mêmes paramètres TK «les plus pessimistes » quels que soient les composés. Enfin, des scenarios prospectifs simples ont été développés pour illustrer ces résultats et les possibles applications du modèle développé.In fine, ces prédictions de la contamination, de la croissance et du développement des soles pourront être reliées, lors de travaux ultérieurs, à des effets potentiels sur les fonctions physiologiques de la sole (modèles DEBtox), et aux conséquences sur la dynamique des populations de soles (e.g.modèles matriciels de population). / Estuarine ecosystems are particularly impacted by global change and, specifically, bychemical pollution from numerous xenobiotics that may be associated to ecotoxicological and health risks. In environmental toxicology and risk assessment, bioaccumulation is a fundamental process as it controls the internal doses of potential toxicants in organisms. However, the contamination and decontamination flows depend on internal processes thatare themselves dependent on environmental conditions (e.g. temperature, food) and thus on the other variables of global change.In this context, this manuscript aims at describing, within a mechanistic modelling framework, the bioaccumulation processes of two families of potentially toxic and bioaccumulable halogenated persistent organic pollutants (POPs) with contrasting physicochemical properties: the polychlorinated biphenyls (PCBs, highly lipophilic historical compounds) and the perfluorinated substances (PFAS, amphiphilic emerging compounds).This work focuses on the Gironde estuary whose nursery function is fundamental for many species of marine fish including the common sole (Solea solea), often used as an indicator of the quality of coastal and estuarine bursary grounds. In order to account for the influence of environmental conditions on bioaccumulation, the first part of this work consisted in developing a toxicokinetic model (TK) coupled with a mechanistic bioenergetic model based on the theory DEB (Dynamic Energy Budget). This DEBmodel has been parameterized for common sole and calibrated for each sex (packageDEBtool). It allows predicting the main evolution of the physiological functions of interest forbioaccumulation (ingestion, growth, reproduction...) throughout the life cycle of an individualaccounting for dynamic environmental conditions. The developed TK model was first calibrated for some PCBs, under controlled conditions, using an innovative method to take into account individual ingestion variability. This work showed that even if the individual ingestion of each fish is accounted for, the effective assimilation of contaminant is very variable and correlated with the lipid levels of the individuals. The application of the model tothe in situ conditions of the Gironde estuary led to identify that, whatever the contaminant family, the composition of the soles diet had a strong influence on the variability of soles contamination and age at sexual maturity. The comparison of model predictions with measurements made in juveniles of the estuary allowed calibrating the TK parameters values for the major compound of each family in the environment (CB153 and PFOS). This calibration led to two observations in the context of a risk assessment: (1) a lack of knowledge to extrapolate calibrations of TK parameters under controlled conditions to natural conditions;(2) the difference in risk assessment error related to the use of the same "worst case" TK parameters regardless of the compounds. Lastly, simple prospective scenarios have beendeveloped to illustrate these results and the possible applications of the model developed.Ultimately, these predictions of soles contamination, growth and development may be related in future work to potential effects on the physiological functions of sole (DEBtox models), and to consequences on soles population dynamics (e.g. matrix population models).

Gestillte Kinder sind über die Muttermilch mit persistenten organischen Schadstoffen (POPs) belastet. Tierexperimentelle Studien deuten auf eine besondere Empfindlichkeit des sich entwickelnden Immunsystems für POPs hin. Mögliche Effekte dieser Verbindungen auf den kindlichen Organismus sind bisher kaum untersucht. Es wurden potenzielle Einflüsse verschiedener POPs (PCDDs, PCDFs, PCBs, beta-HCH, HCB und pp-DDE) auf natürliche Killerzellen (NK-Zellen) und NK-Aktivität bei gestillten im Vergleich zu nicht gestillten Kindern untersucht. NK-Zellen sind eine Lymphozytensubpopulation (CD3-CD56/16+), die über ihre zytotoxische Aktivität allogene, virusinfizierte und maligne Zellen ohne vorherige Sensibilisierung töten kann. Es wurden 66 gesunde Kinder im Alter von 11-12 Monaten untersucht, davon waren 50 Kinder mindestens 4 Monate lang voll gestillt und 16 Kinder nicht gestillt. Aus einer Region mit bekannter erhöhter PCDD/PCDF-Belastung stammten 13 gestillte Kinder. Die NK-Zellzahlen wurden mittels Immunphänotypisierung am Durchflusszytometer bestimmt. Die Aktivität der NK-Zellen wurde mit einem nicht-radioaktiven, durchflusszytometrischen Zytotoxizitäts-Assay gemessen. Die POP-Konzentrationen im Blutfett der Probanden wurden kommerziell bestimmt. Weder bei den NK-Zellzahlen, noch bei der NK-Aktivität konnten zwischen den gestillten und nicht-gestillten Kindern signifikante Unterschiede im t-Test nachgewiesen werden. In Korrelationsanalysen zeigten sich keine signifikanten Einflüsse der POP-Konzentrationen auf NK-Zellzahlen und NK-Aktivität. Im Laufe der Untersuchung zeigte sich, dass der eingesetzte Zytotoxizitäts-Assay nur semiquantitative Daten lieferte. Die vorliegenden Ergebnisse und weitere Befunde bezüglich des Immunsystems der Probanden weisen darauf hin, dass die relativ hohe Belastung lange gestillter Säuglinge mit POPs nicht zu einer biologischen Wirkung im kindlichen Organismus führt. Angesichts der nachgewiesenen positiven Effekte des Stillens, kann diesbezüglich die bestehende Stillempfehlung bekräftigt werden. / Breast-fed infants are exposed to persistent organic pollutants (POPs) via breast milk. Animal studies indicate a special sensitivity of the maturing immune system to POPs. Possible effects of these compounds on the infantile organism are so far barely examined. Potential influences of several POPs (PCDDs, PCDFs, PCBs, beta-HCH, HCB and pp-DDE) on natural killer (NK) cells and NK activity of breast-fed infants in comparison to formula-fed infants were investigated. NK cells are a subset of lymphocytes (CD3-CD56/16+) that can kill allogeneic, virus-infected and malignant cells via their cytotoxic activity without prior sensitization. The study group consisted of 66 healthy infants examined at age 11 to 12 months, of which 50 infants were breast-fed and 16 infants were formula-fed. 13 breast-fed infants came from a region with known increased PCDD/PCDF-burden. Numbers of NK cells were measured by flow cytometric immunophenotyping. NK activity was analysed by a non-radioactive flow cytometric cytotoxicity assay. POP concentrations in the blood fat of the probands were calculated commercially. There were no significant differences between breast-fed and formula-fed infants concerning number and activity of NK cells in the t-test. Analysis of correlation showed no significant influences of POP concentrations on the number and activity of NK cells. In the course of the study the data obtained by the employed cytotoxicity assay proved to be only semiquantitative. The presented findings and further results concerning the immune system of the study subjects suggest that the relatively high burden of long-term breast-fed infants with POPs does not lead to a biological effect in the infantile organism. Regarding the proven positive effects of breast-feeding the existing recommendation to breastfeed can be encouraged.

MENVSC / Department of Hydrology and Water Resources / Sewage sludge (biosolids) from wastewater treatment plants (WWTPs) has been widely used as a soil improver in Europe, United States of America and some developing countries including South Africa. It has its benefits for farmers as a good source of organic matter and minerals, however, sludge after treatment still contains pathogenic organisms, heavy metals and persistent organic pollutants (POPs). The POP and heavy metal contaminants that accumulate in sludge may transfer through the food chain and cause adverse effects on human beings. In this study, a field experiment was carried out on farmland fertilized with sewage sludge from a wastewater treatment plant (WWTP) that vasically receives domestic wastewater and storm water. Vegetable spinach (Spinacia oleracea) was used for this study and was planted on a farmland under controlled conditions. Ten ridges each of dimensions 20 m × 0.3 m was made and dry sludge weights of 5, 10, 15, 20, 25, 30, 35, 40, 45 and 50 kg were applied as manure on each of the ridges, respectively. Representative samples of sludge and soil were taken for analysis of heavy metals and POPs. At maturity, in twelve weeks, the root and leave samples of the vegetable were taken from all the ridges including the control. The soil, sludge, and vegetable samples were analyzed for total heavy metal content (Cd, Cr, Cu, Ni, Pb, Co, Zn, Al, Fe, Mn), speciated heavy metal content and POP (PAH, PCB). Soil and sludge samples were also analyzed for total organic content, pH, cation exchange capacity (CEC), conductivity and alkalinity. The analysis for total heavy metals and speciated heavy metal content was carried out using inductively coupled plasma optical emission spectrophotometer (ICP-OES), and CEC analysis was carried out using atomic absorption spectrophotometer (AAS). A two-dimensional gas chromatograph with time of flight mass spectrometry detector (GC X GC TOFMS) was used for POP measurements. pH measurement was made using a pH meter and conductivity measurement using a conductivity meter. Alkalinity and total organic content analysis was performed using titrimetric apparatus. The highest total heavy metal concentration of 378.9 mg / kg was recorded in Fe metal in soil and Leaf sample while the lowest total metal concentration of 0.0003 mg / kg was in Cu metal in root sample. The highest heavy metal concentration of 1002 mg / kg in speciated forms was in Mn metal in F1 fraction and the lowest of 0.0004 mg / kg was in Cd metal in F5 fraction. PAHs were only found in soil samples and their concentrations ranged from 2.53 mg / kg to 146.5 mg / kg. There were no PCB detected in all the samples analysed. The results indicated that the trace metals concentrations found in the exchangeable fraction were higher than those observed in any of the preceding extractions except in the case of Cd, Cr, Fe and Pb where Fe-Mn oxide and organic matter fractions predominated and were closely followed by exchangeable fraction.