Thesis (M.Sc.)--College of William and Mary. / Vita. Includes bibliographical references. Also available online.

Thesis (Ph. D.)--Oregon State University, 2008. / Printout. Includes bibliographical references. Also available on the World Wide Web.

<p>Over time, the Baltic Sea has been contaminated by increasing discharges of pollutants from human activities. Persistent organic pollutants (POPs) have caused toxic effects in wildlife and excess of nutrients have led to eutrophication. Furthermore, there are indications that certain polyhalogenated compounds similar in structure to man-made POPs are produced by the biota present in this sea. In the late 1990’s both methoxylated polybrominated diphenyl ethers (MeO-PBDEs) and hydroxylated-PBDEs (OH-PBDEs) were identified in fish and seals living in this environment. OH-PBDEs can originate from metabolism of PBDEs, but both OH- and MeO-PBDEs are also known to be natural products in marine environments. Another group of POPs, the polybrominated dibenzo-<i>p</i>-dioxins (PBDDs), are not produced commercially, but are known to be by-products of chemical industry and of the combustion of, e.g., brominated flame retardants (BFRs). In contrast to the OH- and MeO-PBDEs, PBDDs have not previously been shown to be natural products, although certain related compounds have been indicated to have a natural origin.</p><p>This thesis describes the identification of PBDDs, OH-PBDEs and MeO-PBDEs in algae, blue mussels and fish living in the Baltic Sea. Several of these compounds were also detected in cyanobacteria. Moreover, PBDDs were present in fish, mussels, shrimp and crabs from different regions of the Baltic Sea and from the west coast of Sweden, but not in organisms from freshwater environments. The levels of these compounds in Baltic fish generally exceeded those of their chlorinated analogues. The origin of the PBDDs identified is somewhat unclear, but the high levels present in blue mussels and the pattern of congeners observed indicate natural production. The presence of PBDDs, OH-PBDEs and MeO-PBDEs in fish and shellfish constitutes a potential risk to both humans and wildlife and requires further investigation.</p>

Over time, the Baltic Sea has been contaminated by increasing discharges of pollutants from human activities. Persistent organic pollutants (POPs) have caused toxic effects in wildlife and excess of nutrients have led to eutrophication. Furthermore, there are indications that certain polyhalogenated compounds similar in structure to man-made POPs are produced by the biota present in this sea. In the late 1990’s both methoxylated polybrominated diphenyl ethers (MeO-PBDEs) and hydroxylated-PBDEs (OH-PBDEs) were identified in fish and seals living in this environment. OH-PBDEs can originate from metabolism of PBDEs, but both OH- and MeO-PBDEs are also known to be natural products in marine environments. Another group of POPs, the polybrominated dibenzo-p-dioxins (PBDDs), are not produced commercially, but are known to be by-products of chemical industry and of the combustion of, e.g., brominated flame retardants (BFRs). In contrast to the OH- and MeO-PBDEs, PBDDs have not previously been shown to be natural products, although certain related compounds have been indicated to have a natural origin. This thesis describes the identification of PBDDs, OH-PBDEs and MeO-PBDEs in algae, blue mussels and fish living in the Baltic Sea. Several of these compounds were also detected in cyanobacteria. Moreover, PBDDs were present in fish, mussels, shrimp and crabs from different regions of the Baltic Sea and from the west coast of Sweden, but not in organisms from freshwater environments. The levels of these compounds in Baltic fish generally exceeded those of their chlorinated analogues. The origin of the PBDDs identified is somewhat unclear, but the high levels present in blue mussels and the pattern of congeners observed indicate natural production. The presence of PBDDs, OH-PBDEs and MeO-PBDEs in fish and shellfish constitutes a potential risk to both humans and wildlife and requires further investigation.

Thesis (Ph. D.)--College of William and Mary. / Vita. Includes bibliographical references. Also available via the World Wide Web.

Many chemicals off-gas or leech into indoor environments from sources such as consumer products, furnishings, and building materials. An understanding of the pathways from the sources to human exposure is vital in order to implement control strategies and lower exposure. Objects containing Brominated flame retardants (BFRs), one class of semivolatile organic compounds (SVOCs), burn more slowly during combustion. BFRs, especially polybrominated diphenyl ethers (PBDEs), are used in electronic devices including casings and circuit boards. Heat from internal circuitry increases the BFR vapor pressure and the partition coefficient, enhancing its transport out of the substrate and into the indoor environment. In this work, a computer tower in an office setting provides a case study to examine the emissions of, and exposure to, PBDEs. the case of a computer tower, the cooling fan increases the mass transfer coefficient, further increasing emissions. During computer use, the emission rate of PBDEs from the interior of the case is more than double the emission rate from the exterior of the case due to elevated internal temperatures and higher mass transfer due to the cooling fan. The concentration of PBDEs in the room air increases 40 - 80% for every 5°C increase inside the computer case, depending on the PBDE congener. Such enhanced emissions are a concern since recent studies have shown adverse health effects of PBDEs on human health. The major contributions of this work are: A model was developed that is useful for SVOC emissions for various heat and mass transfer situations, including diffusion through the slab and convective boundary conditions on each side of the slab, which may be simplified if the situation warrants; A systematic propagation of the uncertainties and variability of the model parameters was accomplished by using a Monte Carlo method for the input of the parameters into the model; A polydisperse indoor particle distribution was used as a sink, identifying the size-discretized particle phase PBDE concentration; An exposure assessment showed that the inhalation pathway for PBDEs in the gas and particulate phases is relevant and that the particulate phase exposure is dominant. / text

Thesis (doctoral)--Stockholm University, 2004. / Cover title. Includes bibliographical references (p. 59-69).

Thesis (Ph. D.)--University of Texas at Austin, 2008. / Vita. Includes bibliographical references.

Brominated flame retardants have been widely used in industry. There is a rapidly growing public concern about their ubiquity in the environment. This project investigated the possible removal treatments of polybrominated diphenyl ethers (PBDEs) using two treatment methods: (I) photocatalysis by TiO2 and (II) phytoremediation by Oryza sativa and Phragmites australis, and a combined system involving these two technologies. Advanced oxidation process (AOP) is a promising technology for removing emerging chemicals. In this case, nano-scaled titanium (IV) oxide was applied to evaluate its capability in the degradation of BDE-209 under visible light. The residual PBDE congeners after reaction were analyzed by gas chromatography-mass spectrometry (GC-MS). The half-life for removing BDE-209 by TiO2 was 3.05 days under visible light. Tetra- and penta-BDEs were the major degraded products of BDE-209. Optimum conditions for photocatalytical degradation of BDE-209 was found to be pH 12 (93% ± 1%), at least 5 mg/L (93 ± 1.70%) of humic acid and in the form of anatase/rutile TiO2 (82% ± 3%). Incomplete removal of PBDEs by water treatment plants and point-source contamination may lead to their discharge into water bodies and ultimately into soils. Consequently, the second part of the project was phytoremediation of PBDEs. Uptake of BDE-209 by rice cultivars, namely Fengmeizhan, Hefengzhan and Guangyinzhan, and common reed were examined by 60-day cultivation in sterilized BDE-209 spiked soil. Hefengzhan possessed the greatest ability in the removal and accumulation of BDE-209 among the three cultivars, especially when associated with Glomus intraradices, at pH 7. A series of plant-contamination sorption analyses were also employed for pathway studies of PBDEs uptake by rice. A partition-limited model was applied for describing and estimating the uptake of BDE-209 by rice roots. The average quasi-equilibrium factors (apt) of BDE-47, -99 and -209 in root uptake were 1.44 × 10-3 , 0.966 × 10 -3 and 0.115 × 10-3 in sand (< 1), implying a non-equilibrium state of the movement of molecules and a dominant passive transport uptake. From the result of sorption analysis of dead and fresh roots, the apoplastic pathway likely dominated the transport of PBDEs into root cells. These results provide essential information on the uptake mechanism of PBDEs into plants. Based on the results from photocatalysis and phytoremediation, a combined photocatalysis (TiO2 and visible light) and constructed wetland system (Oryza sativa (Hefengzhan) and Phragmites australis (common reed) was set up for comparing PBDEs removal efficiencies. The removal percentages of BDE-209 in the combined system were found to be promoted when compared to the individual systems, which could be explained by enhanced biodegradability of PBDEs in photocatalysis. Therefore, the proposed advanced wastewater treatment technology (combined photocatalysis and constructed wetland systems) might help to degrade and eliminate BDE-209 in the wastewater, and thus reduce the risks of marine contamination by discharging these incompletely or partially treated wastewaters containing PBDEs.

Based on the findings from breast cancer cells and nude mouse assays, we noticed that fatty acid metabolism was influenced by BDE-47 exposure. To have a comprehensive understanding of the impact, we performed targeted metabolomics analysis of fatty acids. Short-chain fatty acids (SCFAs) and hydroxylated short-chain fatty acids (OH-SCFAs) are crucial intermediates related to a variety of diseases, such as bowel disease, cardiovascular disease, renal disease and cancer. We developed a global profiling method to screen SCFAs and OH-SCFAs by tagging these analytes with d0/d6-N, N-dimethyl-6,7-dihydro-5H-pyrrolo[3,4-d] pyrimidine-2-amine (d0/d6-DHPP) and UHPLC-MS/MS in parallel reaction monitoring (PRM) mode. The derivatization procedure was simple and rapid. The targeted compounds could be derivatized within three minutes under mild condition and analyzed without the need of further purification. The derivatization significantly improved the chromatographic performance and mass spectrometry response. The d6-DHPP tagged standards were used as internal standards, which remarkably reduced the matrix effects. The use of high resolution PRM mode made it possible to identify unknown SCFA and OH-SCFA species. The developed method was successfully applied to the analysis of mouse feces, serum, and liver tissue samples harvested from the breast cancer nude mice that had been exposed to BDE-47. By using the developed method, 40 analytes (10 SCFAs and 30 OH-SCFAs) were characterized. Semi-quantitative analysis indicated that the exposure of BDE-47 to the mice altered the SCFA and OH-SCFA metabolism, especially in the high dose group. In addition, medium- and long-chain fatty acids (MLFAs) are essential energy sources in cells and possess vital biological functions. Characteristics of MLFAs in biosamples can contribute to the understanding of biological process and the discovery of potential biomarkers for relevant diseases. However, there are obstacles of the MLFAs determination because of the poor ionization efficiency in mass spectrometry and structural similarity. Herein, a derivatization strategy was developed by labeling with d0-DHPP and detecting with UHPLC-MS/MS in multiple reaction monitoring (MRM) mode. The parallel isotope labeled internal standards were generated by tagging d6-DHPP to MLFAs. The simple and rapid derivatization procedure and mild reaction conditions greatly reduced the potential of MLFA degradation. With the methodology, the chromatography performance was greatly improved, and the mass spectrum response was enhanced up to 1, 600 folds. Finally, the developed derivatization method was applied to serum samples to analyze the alteration of MLFAs induced by BDE-47 exposure in breast cancer nude mice. The semi-quantitative results demonstrated that the BDE-47 exposure significantly influenced the MLFA metabolism. Together, mass spectrometry-based targeted and nontargeted metabolomics of in vitro and in vivo studies suggested that BDE-47 impacted multiple metabolic pathways and was positively associated with breast tumor growth in mice. This study might further our understanding of the health risks of BDE-47 to breast cancer.;Polybrominated diphenyl ethers (PBDEs) are commonly used to prevent the development of fire in various factory products. Due to the adverse effects on human health and bio-accumulation capacity, PBDEs are considered as one kind of persistent organic pollutants. 2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) is one of the most frequently detected PBDE congeners in humans. Although numerous studies have shown the close connection between BDE-47 and human health, few reports were related to breast carcinoma. In vivo study of the association between BDE-47 and breast cancer was also scarce. In this study, both in vitro and in vivo experiments were conducted to explore the influence of BDE-47 to breast cancer. Firstly, we performed the in vitro study by exposing different concentrations of BDE-47 (5, 10 µM) to MCF-7 breast cancer cells. Nontargeted metabolomics analysis was conducted by using ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS). Results showed that the toxicity to MCF-7 cells gradually increased when the concentration of BDE-47 exceeded 1 µM in the medium. Pyrimidine metabolism, purine metabolism and pentose phosphate pathway (PPP) were the most influenced metabolic pathways, and the metabolites in the three metabolic pathways were significantly downregulated. Moreover, the increase of reactive oxygen species was detected by using the 2',7'-dichlorodihydrofluorescein diacetate staining assay. Results suggested that the BDE-47 induced oxidative stress by downregulating the NADPH generation in PPP. The pyrimidine metabolism and purine metabolism might be downregulated by the downregulation of mRNA transcripts. Therefore, BDE-47 could induce oxidative stress in breast cancer cells by inhibiting PPP and disordering the metabolism of the entire cell subsequently. Secondly, we constructed a breast cancer nude mouse model, performed in vivo exposure of BDE-47 to the mice, and conducted mass spectrometry-based metabolomics and lipidomics analysis to investigate the metabolic changes in mice. Results showed that the tumor sizes were positively associated with the dosage of BDE-47. Metabolomics and lipidomics profiling analysis indicated that BDE-47 induced significant alterations of metabolic pathways in livers, including glutathione metabolism, ascorbate and aldarate metabolism, and lipids metabolism, etc. The upregulations of phosphatidylcholines and phosphatidylethanolamines suggested the membrane remodeling, and the downregulations of Lyso-phosphatidylcholines and Lyso-phosphatidylethanolamines might be associated with the tumor growth. Targeted metabolomics analysis revealed that BDE-47 inhibited fatty acid β-oxidation (FAO) and induced incomplete FAO. The inhibition of FAO and downregulation of PPARγ would contribute to inflammation, which could promote tumor growth. In addition, BDE-47 elevated the expression of the cytokines TNFRSF12A, TNF-α, IL-1β and IL-6, and lowered the cytokines SOCS3 and the nuclear receptor PPARα. The changes of cytokines and receptor may contribute to the tumor growth of mice.