Os éteres de bifenilas polibromados (PBDEs) são largamente usados como retardadores de chama e têm sido detectados no sangue humano, tecido adiposo e leite materno devido às suas propriedades físico-químicas e bioacumuladoras e à sua elevada persistência no meio ambiente. Muitos estudos têm relatado toxicidade hepática relacionada à exposição aos PBDEs. Como efeitos citotóxicos são frequentemente associados à disfunção mitocondrial,no presente estudo, investigamos a toxicidade do BDE-47 em mitocôndrias isoladas de fígado de rato. Nos seguintes parâmetros: potencial de membrana mitocondrial, consumo de oxigênio, interação com a membrana mitocondrial, liberação de cálcio, inchamento mitocondrial e os níveis de ATP da suspensão mitocondrial com a finalidade de observar a capacidade do composto em interferir com a bioenergética da organela. Avaliou-se ainda a formação de espécies reativas de oxigênio (ROS), dos níveis de GSH/GSSG, níveis mitocondriais de grupos sulfidrila de proteínas e níveis mitocondriais de NAD(P)H com o intuito de analisar o estado redox mitocondrial. Os congêneres BDE-47 e BDE-99 foram avaliados em concentrações que variaram entre 0,1 e 50 ?mol/L. Os dois congêneres de PBDEsapresentaram toxicidade mitocondrial afetando todos os parâmetros que avaliam a bioenergética mitocondrial culminandoum uma depleção do ATP. Por outro lado, nos ensaios de avaliação do estresse oxidativo os PBDEs estudados não demonstraram qualquer efeito, no entanto, afetaram a cadeia respiratória mitocondrial, o que normalmente reflete em um acúmulo de espécies reativas de oxigênio. Estes resultados são explicados pelo mecanismo de ação destes compostos como retardante de chama, pois durante a combustão os retardantes de chama bromados realizam a neutralização de radicais livres (OHo e Ho). Conclui-se assim que os PBDEs podem levar à disfunção bioenergética e assim induzir a morte celular pela diminuição do ATP. Observou-se ainda que BDE-47 apresentou maior toxicidade do que o BDE-99 sobre os parâmetros estudados. / Polybrominated biphenyls ethers (PBDE) , widely used as flame retardants, have been detected in human blood, adipose tissue and breast milk due to their physicochemical and high bioaccumulative properties and environmental persistence. Many studies have reported liver toxicity related to exposure to PBDEs. As cytotoxic effects are often associated with mitochondrial dysfunction,in the present study, we investigated the toxicity of the BDE-47 and BDE-99 on isolated rat liver mitochondria. Assessing mitochondrial membrane potential, oxygen consumption, interaction with the mitochondrial membrane, calcium release, mitochondrial swelling and ATP levels of the mitochondrial suspension in order to observe the ability of the compounds to interfere with the bioenergetic organelle, and the formation of reactive oxygen species (ROS), GSH/GSSG levels, mitochondrial sulfhydryl groups and levels of mitochondrial NAD(P)H in order to analyze mitochondrial redox state. The congeners BDE-47 and BDE -99 were evaluated at concentrations ranging between 0.1 and 50 ?mol/L. Both PBDEs congeners showed mitochondrial toxicity affecting all parameters that assess mitochondrial bioenergetics and culminating with ATP depletion. On the other hand, no effect was observed in tests assessing oxidative stress, although they were able to inhibit the mitochondrial respiratory chain, which is usually reflected in an accumulation of reactive oxygen species. These results are explained by the mechanism of action of this compounds as flame retardants, because during the combustion brominated flame retardants perform the neutralization of free radicals (OHo and Ho). It follows that PBDEs can lead to mitochondrial dysfunction and thus induce bioenergetic cell death. It was also observed that The BDE-47 showed higher toxicity than BDE-99 in the studied model

Thesis (Ph. D.)--Oregon State University, 2007. / Printout. Includes bibliographical references (leaves 102-117). Also available on the World Wide Web.

Os retardantes de chama bromados são substâncias utilizadas nos mais variados bens de consumo para aumentar sua resistência ao fogo e/ou altas temperaturas em casos de incêndio, aumentando assim, as chances de escape e reduzindo a gravidade das queimaduras. Para este fim os éteres difenílicos polibromados (PBDEs) representam a classe mais utilizada tendo em vista sua eficiência no controle da propagação da chama e seu baixo custo. Estes compostos se incluem entre os recentemente denominados contaminantes ambientais emergentes que apresentam uma carência de dados toxicológicos, principalmente em relação aos efeitos danosos e aos biomarcadores de exposição, além do potencial dano ao ambiente, sendo esta uma preocupação recente da comunidade científica. Pelo fato da mitocôndria ser reconhecida como a principal organela produtora de energia celular, além de exercer um papel fundamental na manutenção de inúmeras funções celulares, ela foi utilizada como modelo experimental para avaliar os efeitos dos congêneres de BDE- 100; -153; -154 e -209 na faixa de concentração de 0,1 ?mol/L a 50 ?mol/L. Nossos resultados mostram que os efeitos em mitocôndrias isoladas podem ocorrer em menores concentrações para os congêneres BDE-153; -154 (Hexa-BDE) e -209 (Deca-BDE) e em maiores concentrações para o BDE-100 (Penta-BDE). Desta forma, foi observado que os compostos possuem capacidade de interagir com membrana mitocondrial, induzir inchamento mitocondrial, desregular a homeostase cálcica e dissipar o potencial de membrana mitocondrial em concentrações diferentes, entretanto não são capazes de induzir estresse oxidativo na mitocôndria. Assim, os resultados indicam que a ação dos PBDEs sobre mitocôndrias pode ser um dos mecanismos de toxicidade desta classe de compostos. / The brominated flame retardants are substances used in various consumer goods to increase their fire resistance and / or higher temperatures in case of fire, thus increasing the chances of escape and reducing the severity of burns. To this end polybrominated diphenyls ethers (PBDEs) are the most used class in view of its efficiency in controlling the spread of flame and its low cost. These compounds are among the newly emerging environmental contaminants known to exhibit a lack of toxicological data, especially regarding the harmful effects and biomarkers of exposure and potential harm to the environment, which is a recent concern of the scientific community. Because the mitochondrion is recognized as the main energy-producing cell organelles, as well as play a vital role in the maintenance of many cellular functions, it was used as an experimental model to evaluate the effects of the congeners BDE-100 (Penta- BDE), -153, -154 (Hexa-BDE) and -209 (Deca-BDE), in concentration range ranging from 0.1 ?mol/L to 50 ?mol/L. The results show that the effects on isolated mitochondria may occur at lower concentrations for the BDE-153, -154 and -209 and high concentrations to the BDE-100. Thus, it was observed that the compounds have the ability to interact with mitochondrial membrane, inducing swelling, dysregulation of calcium homeostasis and dissipation of membrane potential at different concentrations, however they cannot change factors related to oxidative stress in mitochondria. Furthermore, the induction of mitochondrial swelling, and added significant depletion of ATP levels may contribute to the toxic effects observed. Thus, we conclude that the action of PBDESS on mitochondria is one of the mechanisms of toxicity of this class of compounds.

Background & Objectives: This dissertation is comprised of two independent projects that seek to answer the research questions outlined in Aims 1 and 2. The first project is focused on measuring exposure to polybrominated diphenyl ethers (PBDE) throughout the early lifecourse, as well as investigating how exposure at different developmental periods relates to neuroendocrine endpoints. PBDEs are flame retardant chemicals that were used extensively in furniture and furnishings sold throughout the United States until their phase-out in 2004. Human exposure occurs primarily through incidental ingestion of PBDE-contaminated dust present in the indoor environment. The second project aimed to characterize telomere dynamics in maternal-child pairs and to evaluate associations between telomere dynamics and indicators of stress and stressful conditions. Telomeres are non-coding nucleotide repeats located at chromosome ends; they serve several functions, such as buffering against loss of important protein coding DNA regions during cell division. Both projects are focused on exposure-response relationships during early life and a central theme throughout this dissertation relates to the intersection of date, time and age in longitudinal cohort studies. Finally, the third aim seeks to integrate findings from Projects I and II and is focused on investigating whether telomere dynamics can be used as a biological indictor of stress in epidemiological research examining associations between low-level environmental chemical exposures and neurodevelopmental endpoints. Methods: Both projects were conducted using data and samples collected as part of the Columbia Center for Children’s Environmental Health (CCCEH) Mothers and Newborns study. In Project I, PBDEs were measured by the Centers for Disease Control and Prevention (CDC) using gas chromatography-mass spectrometry (GC-MS) in plasma samples collected repeatedly between birth and age 9 years. We examined determinants of 1) prenatal exposure to PBDEs (Chapter 2), and 2) trajectories of PBDE exposure over childhood, which we estimated using latent class growth analysis (LCGA) (Chapter 3). We also examined PBDE trajectories in relation to performance on tests of visual, verbal and working memory among early adolescents (Chapter 4) and investigated associations between prenatal exposure to PBDEs and thyroid hormone parameters, which were measured by radioimmunoassay in plasma samples collected at multiple ages (Chapter 5). In Project II, we used monochrome multiplex quantitative polymerase chain reaction (MMqPCR) to measure relative leukocyte telomere length (rLTL) in samples collected from mothers and newborns (umbilical cord blood) at the child’s delivery and from children at ages 2, 3, 5, 7 and 9-years (Chapter 6). We aimed to characterize rLTL dynamics over early life, examine the correlation between paired maternal-newborn rLTL, and examine associations between rLTL with measures of financial strain, perceived stress and maternal distress. Results: In Project I, we detected PBDEs in over 80% of cord blood samples and in multivariable models, sociodemographic and lifestyle factors explained 12% of cord blood PBDE variability. The largest determinant of exposure was ethnicity, with Dominican newborns having lower exposure compared to African American newborns, likely due to the reduced amount of time Dominican mothers had spent in the United States when they gave birth to the study child. Across postnatal life (2000 to 2013), PBDE concentrations in child blood decreased by approximately 12% per year, suggesting that exposure has continually declined since the PBDE phase-out in 2004. Trajectory analyses revealed several unique patterns of PBDE exposure over the early lifecourse, with the majority of children characterized by exposure that was persistently low or that peaked during toddler years. Smaller groups of children were characterized by exposure that was highest during the prenatal period and decreased after birth or by a pattern of high exposure during toddler years that remained elevated into middle childhood. We identified several important predictors of childhood PBDE exposure patterns, including modifiable factors, such as cleaning behaviors. In relation to neurodevelopmental outcomes, we found that children with sustained high exposure to PBDEs scored approximately 5-8 points lower on tests of visual memory. Associations between prenatal exposure and working memory significantly varied by sex, with inverse associations (approximately 8 points lower) observed only among girls. Children with PBDE plasma concentrations that peaked during toddler years performed better on verbal domains, however, these associations were significant only among children breastfed for more than 12 weeks. Finally, in relation to thyroid hormone levels, children with BDE-47 concentrations in the third and fourth quartiles of the exposure distribution (versus first quartile) had significantly lower TSH and free T4 levels, respectively. We did not detect associations between BDE-47 and total T4 levels; likewise, we did not detect associations between other pentaBDE congeners and any thyroid parameter. In Project II, we found that maternal-newborn rLTL in paired samples was moderately correlated and that maternal rLTL at delivery explained 8% of the variability (R2) in newborn rLTL. In relation to measures of hardship, perceived stress and demoralization, we found an inverse, albeit not statistically significant, association between maternal perceived stress and newborn rLTL. We did not detect an association with maternal rLTL, nor did we detect associations between material hardship or demoralization and maternal or newborn rLTL. When examining rLTL in child blood samples collected between birth and age 9 years, we observed a U-shaped pattern characterized by rapid shortening of rLTL between birth and 2 years, followed by gradual lengthening between ages 3 and 9 years. It remains unresolved whether this pattern reflects a true biological phenomenon or if it is an artifact of measurement error introduced by analytic or pre-analytic conditions. Conclusions: Despite the phase-out of PBDEs in 2004, exposure among children residing in New York City remained nearly ubiquitous through 2013, however, concentrations did decline over time. Our finding of several PBDE trajectories suggests that, despite the relatively long half-lives of PBDEs, a single measure may not accurately reflect exposure throughout childhood. Our findings of reduced scores on tests of working and visual memory during the prenatal and postnatal periods, respectively, support a growing body of literature linking early life PBDE exposure to disrupted neurodevelopment. The results of our analysis examining thyroid hormone disruption during childhood revealed a pattern consistent with hypothalamic or pituitary-level disruption during prenatal programming of the thyroid regulatory system. This is the first study to examine prenatal PBDE exposure in relation to childhood thyroid hormone levels, therefore, it is important that this finding is replicated by future research. Our finding of an inverse association between newborn rLTL and maternal perceived stress is consistent with results from previous research and suggests that the developing fetus may be sensitive to maternal stress perception during pregnancy, however, additional research is needed to more fully understand the mechanisms through which this transmission occurs. Our finding of increasing telomere length between toddler years and middle childhood is unexpected and raises questions about the suitability of the qPCR assay for analyzing telomere length in archived samples. Additional analyses are needed to determine whether the observed patterns reflect true biological changes or relate to measurement error introduced during sample processing, storage or analysis. Given these outstanding issues, we were ultimately unable to draw conclusions about the usefulness of telomere dynamics as a stress-sensitive biomarker.

<p>Brominated flame retardants (BFRs) are a diverse group of chemicals, which are used to slow down or inhibit the development of fires. BFRs are incorporated into a wide range of consumer products that are considered as potential fire hazards, such as TV-sets, household appliances, computers, and textiles. The production and use of BFRs is extensive and consists of mainly tetrabromobisphenol A (TBBPA), polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecan (HBCD). BFRs in general, but in particular the PBDEs, have led to both scientific and public concern since they have been found to bioaccumulate in humans and wildlife. The general population is targeted by the PBDEs due to their applications and via the food web. Occupational exposure occurs not only during direct handling of BFRs, but also during handling, repair and dismantling of flame retarded goods.</p><p>This thesis is aimed to assess occupational exposure to BFRs. It is mainly focused PBDEs and especially the PBDEs with high bromine content, such as decabromodiphenyl ether (BDE-209). The work has been accomplished by analysis of BFRs in indoor air at industries handling BFRs or flame retarded goods, and by analysis of blood drawn from workers with potential exposure to BFRs. A referent group, abattoir workers with no occupational exposure to PBDEs, was also investigated. Data from these cross-sectional investigations and from serum sampling during vacation in PBDE-exposed workers have been used for calculation of apparent halflives of hepta- to decaBDE in serum.</p><p>The results clearly show that the workers were exposed to PBDEs when handling PBDE containing products or goods. The serum PBDE levels in computer technicians were found to correlate to the estimated cumulative work hours with computers. Exceptionally high concentrations of BDE-209, almost up to 300 pmol/g lipid weight (l.w.) were observed in serum from rubber workers manufacturing or handling rubber compound that was flame retarded with a technical mixture of decabromodiphenyl ether (DecaBDE). Elevated concentrations of PBDEs with eight or nine bromine substituents were also observed. In an electronics dismantling plant, where elevated levels of PBDEs previously had been observed, reduced serum levels of some, but not all PBDE congeners were observed after industrial hygiene improvements. Notably, it was observed that the BDE-209 concentrations in referents with no occupational exposure were similar to the concentrations of 2,2’,4,4’- tetrabromodiphenyl ether (BDE-47), often referred to as the most abundant PBDE congener in humans and wildlife. Additionally, PBDEs with high bromine content were found to have a fast rate of elimination or transformation in humans, based on serum analysis. BDE-209 had an apparent half-life in serum of only 15 days.</p><p>The possibility of quantifying BFRs, such as PBDEs, in human serum at low levels of detection has been achieved by reducing the contamination of the samples and procedural blanks. Major efforts have been done to develop routines and clean up methodology to enable an almost contamination-free environment at the laboratory. The use of a clean room has decreased PBDE levels in the blanks to acceptable limits. The modifications of the original analytical method have made it possible to quantify almost all PBDE congeners of interest in one GC/MS run.</p><p>Occupational and general background exposure of BFRs to humans will continue as long as these chemicals are a part of our daily life and present as environmental contaminants. The present scientific knowledge of the potential health risks of these BFRs still needs to be further developed. It should be stressed that health effects to PBDEs have not been assessed in this work. It is the author's wish that this thesis should add another piece of knowledge to the puzzle of BFRs and BFR exposure to humans and that these data will be used in future risk assessments of PBDEs in particular.</p>

Brominated flame retardants (BFRs) are a diverse group of chemicals, which are used to slow down or inhibit the development of fires. BFRs are incorporated into a wide range of consumer products that are considered as potential fire hazards, such as TV-sets, household appliances, computers, and textiles. The production and use of BFRs is extensive and consists of mainly tetrabromobisphenol A (TBBPA), polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecan (HBCD). BFRs in general, but in particular the PBDEs, have led to both scientific and public concern since they have been found to bioaccumulate in humans and wildlife. The general population is targeted by the PBDEs due to their applications and via the food web. Occupational exposure occurs not only during direct handling of BFRs, but also during handling, repair and dismantling of flame retarded goods. This thesis is aimed to assess occupational exposure to BFRs. It is mainly focused PBDEs and especially the PBDEs with high bromine content, such as decabromodiphenyl ether (BDE-209). The work has been accomplished by analysis of BFRs in indoor air at industries handling BFRs or flame retarded goods, and by analysis of blood drawn from workers with potential exposure to BFRs. A referent group, abattoir workers with no occupational exposure to PBDEs, was also investigated. Data from these cross-sectional investigations and from serum sampling during vacation in PBDE-exposed workers have been used for calculation of apparent halflives of hepta- to decaBDE in serum. The results clearly show that the workers were exposed to PBDEs when handling PBDE containing products or goods. The serum PBDE levels in computer technicians were found to correlate to the estimated cumulative work hours with computers. Exceptionally high concentrations of BDE-209, almost up to 300 pmol/g lipid weight (l.w.) were observed in serum from rubber workers manufacturing or handling rubber compound that was flame retarded with a technical mixture of decabromodiphenyl ether (DecaBDE). Elevated concentrations of PBDEs with eight or nine bromine substituents were also observed. In an electronics dismantling plant, where elevated levels of PBDEs previously had been observed, reduced serum levels of some, but not all PBDE congeners were observed after industrial hygiene improvements. Notably, it was observed that the BDE-209 concentrations in referents with no occupational exposure were similar to the concentrations of 2,2’,4,4’- tetrabromodiphenyl ether (BDE-47), often referred to as the most abundant PBDE congener in humans and wildlife. Additionally, PBDEs with high bromine content were found to have a fast rate of elimination or transformation in humans, based on serum analysis. BDE-209 had an apparent half-life in serum of only 15 days. The possibility of quantifying BFRs, such as PBDEs, in human serum at low levels of detection has been achieved by reducing the contamination of the samples and procedural blanks. Major efforts have been done to develop routines and clean up methodology to enable an almost contamination-free environment at the laboratory. The use of a clean room has decreased PBDE levels in the blanks to acceptable limits. The modifications of the original analytical method have made it possible to quantify almost all PBDE congeners of interest in one GC/MS run. Occupational and general background exposure of BFRs to humans will continue as long as these chemicals are a part of our daily life and present as environmental contaminants. The present scientific knowledge of the potential health risks of these BFRs still needs to be further developed. It should be stressed that health effects to PBDEs have not been assessed in this work. It is the author's wish that this thesis should add another piece of knowledge to the puzzle of BFRs and BFR exposure to humans and that these data will be used in future risk assessments of PBDEs in particular.

Source: Masters Abstracts International, Volume: 47-06, page: 3476. Adviser: Arnold J. Schecter. Includes bibliographical references.

Polybrominated diphenyl ethers (PBDEs) are a widely used class of flame retardants that are important sources for contamination in the marine environment. Sediments serve as a large reservoir for PBDEs due to their large sorption capacity. This research assessed the presence and distribution of PBDEs in Hillsborough Bay, a subdivision of Tampa Bay, FL, by determining levels in surface sediment samples, creating a historical profile of the contaminant in a sediment core taken from within the bay, and investigating sediment characteristics that control their distribution. Compositional patterns and temporal distributions of 8 of the 209 congeners of PBDEs (BDE-28, -47, -99, -100, -153, -154, -183 and 209) were determined in sediment surface samples and a sediment core collected throughout the study area. Contaminant concentrations varied spatially due to proximity to sources and the spatial variability of physical processes that suspend or remove contaminants from the water column. Concentrations in the bay also varied in time with factors such as wind, precipitation, and subsequent freshwater runoff. PBDE contamination in surficial sediments from various regions of Tampa Bay is not well correlated with sediment grain size or organic matter content, but these factors may be more important in suspended sediments which may control the fate of these contaminants in the bay. The results from this investigation can be used in understanding the extent of PBDE pollution, identifying sources, as well as implementing management strategies for Hillsborough Bay.

The fate and bioaccumulation of a contaminant entering the marine environment through wastewater outfalls depends on the contaminant’s persistence and affinity for particles. The physical characteristics of the receiving environment, e.g. current velocity, sedimentary processes, and the availability of organic carbon are also important. However, these latter effects are not usually evaluated quantitatively. This thesis investigates the near-field accumulation in sediment and biota of particle-reactive polybrominated diphenyl ethers (PBDEs) entering coastal waters via two municipal outfalls: one discharging into a high energy, low sedimentation environment near Victoria, B.C., Canada; the other into a low energy, high sedimentation environment near Vancouver, B.C. We used 210Pb profiles in sediment box cores together with an advection-diffusion model to determine surface mixing and sedimentation rates, and to model the depositional history of PBDEs at these sites. A particularly important finding of this study is that the very high energy environment to the southeast of the Victoria outfall accumulates PBDEs despite not having net sediment accumulation. Although the discharge of PBDEs was much lower from the Victoria outfall than from Vancouver, some sediment PBDE concentrations were higher near Victoria. Most PBDEs were dispersed beyond the near-field at both sites, but a greater proportion was captured in the sediment near the Vancouver outfall where rapid burial was facilitated by inorganic sediment supplied from the nearby Fraser River. Clearly, treating wastewater to the same level, regardless of local oceanographic conditions, will not result in a uniform environmental footprint. Total PBDE concentrations in benthic invertebrate communities were higher near Vancouver than Victoria, despite lower concentrations in sediments, and correlated with organic carbon normalized sediment concentrations. Principal Components Analysis suggested uptake of individual PBDE congeners was determined by sediment properties (TOC, grain size), whereas PCB congener uptake was governed by physico-chemical properties (octanol-water partitioning coefficient). Our results suggest that sediment quality guidelines for PBDEs and likely PCBs may be more relevant if corrected to TOC content in sediment. In addition, where enhanced wastewater treatment increases the ratio of PBDEs to particulate organic carbon in effluent, nearfield benthic invertebrates may face increased PBDE accumulation. This underlines the need for source control of persistent organic contaminants, which cannot be broken down by conventional wastewater treatment. / Graduate

Summary Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants. The addition of these chemicals to electrical and electronic equipment, building materials, carpet and textiles reduces flammability and therefore harm and destruction caused by unwanted fire. These chemicals are now internationally ubiquitous in the environment and humans because of their increased usage and physical and chemical properties of persistence and lipophilicity. Although Australian data on both the concentrations and the sources and exposure pathways was limited, a preliminary study of PBDEs in 10 pools of human blood serum revealed that concentrations of PBDEs in Australia were comparatively higher than most countries with the exception of Canada and the USA. The aim of this project was to determine the concentrations of PBDEs in the Australian population and to examine the possible sources and pathways of exposure in humans. Experimental evaluation of PBDE exposure matrices included samples of: sediment (n=46), air (n=19), dust (n=19), surface wipes (n=10) and human milk (157 samples combined into 17 pools, n=10 individual samples); and the general population using human blood serum (10552 samples combined into 169 pools). With accumulating evidence regarding age differences in PBDE concentrations, the scope of this project was broadened to include a focus on infants and young children. This study found that PBDE contamination was widespread in the Australian environment and human population. In sediment, PBDEs were relatively low at the majority of sites with mean ± standard deviation and median ΣPBDE concentrations across all sites of 4707 ± 12580 and 305 pg g-1 dw, respectively. There were elevated concentrations found downstream of sewerage treatment plants; in areas dominated by industrial and urban land-use types; and in estuarine compared to freshwater environments. PBDEs were detected in air, dust and surface wipes. Concentrations on the whole were found to be higher indoors compared to outdoors and in offices compared to homes. ΣPBDE concentrations ranged from 0.5 -179 pg/m3 for homes and 15 - 487 pg/m3 for offices and at the two outdoor sites the concentrations were 1.7 and 6.8 pg/m3. PBDEs were detected on 9 out of 10 surfaces (e.g. television, refrigerator, DVD player) sampled and ranged from non-detectable to 5985 pg/cm2 while in dust, ΣPBDEs ranged from 87 - 733 ng/g dust in homes and 583 - 3070 ng/g dust in offices. PBDEs were detected in all individual and pooled samples of human milk and blood serum and the ΣPBDE and BDE-47 concentrations ranged from 5.5 to 103 and 0.6 to 55 ng/g lipid, respectively. There were no regional differences in concentrations in human milk or blood serum and in general PBDE concentrations were higher in males than in females. Although no temporal trend was apparent in samples of human milk or blood serum collected between 2002 and 2008, the ban on penta- and octa-BDE commercial products in several countries has only been in place since 2004. Hence, effects of the ban may not be reflected in human body burden for several years. The concentrations of PBDEs were found to be highest in young children aged 2 – 5 years of age where concentrations were up to 10 times greater than those detected in adults. Congener profiles for sediment, air, dust and surface wipes were mostly dominated by BDE-209. In human milk and serum, BDE-47 was dominant while BDE-209 contributed only 3% in human milk and was not determined in serum. Concentrations of PBDEs found in Australian human and environmental samples were lower than those reported from North America but higher than those reported from Europe and Asia. The results of modeling and the assessment of matched samples of human milk, indoor air and dust showed that body burden could be partly explained by exposure via food, air, dust and human milk as well as clearance (half-life) data. However, the higher than expected concentrations in young children indicated that there are likely to be missing sources and exposure pathways and/ or the clearance data is inaccurate. The results of this thesis provide baseline data on PBDE concentrations in Australia and will prove important for long term monitoring of the effect of changes in usage rates of these chemicals. It is important to understand the specific sources and exposure pathways of PBDEs in infants and young children in order to identify intervention methods whereby exposure to this vulnerable population can be reduced. In terms of the future use of PBDEs or other flame retardant chemicals, it is important that the risk-benefit ratio is regulated so that the minimization of human exposure and potential associated negative health effects is balanced with the reduction of harm caused by fire.