Fire presents a great risk to humans and their possessions. Polymeric compounds are highly flammable and compounds are added to increase their fire resistance. These additives are referred to as flame retardants. Intumescent flame retardants are systems that form a carbon rich foam on the surface of the polymer during thermal degradation. A new field of metal catalysed intumescence is discussed in this document. The influence of both the metal ion and organic backbone of polyhydroxylcarboxylic acid metal salts was studied. The intumescence and foaming properties of selected salts were studied in more detail. Gluconic acid proved to be the best intumescent and showed the best combination of carbon char yield, foam structure and volume, stability and open flame characteristics. As a general rule of thumb, the char volume and structure improved with an increased number of hydroxyl groups in the compound. Carbon char yield increased with an increase in the number of hydroxyl groups for a constant number of carbons in the complex. The number of acid groups in the compound played a lesser role in intumescence. Most metal complexes catalyse intumescent decomposition of polyhydric compounds such as polyhydroxylcarboxylic acids and pentaerythritol. The reduction in the volatilisation losses implies that the metal cations catalyse carbonisation reactions in the polyhydroxyl compound. Unfortunately, the resultant carbon-foams are unstable: the metal residues also catalyse the further oxidative degradation of the char. The low thermal stability of the compositions tested, as well as the afterglow effect makes them unsuitable for use as flame retardant additives in plastics. From the studies of the different metal complexes with acetylacetone and gluconic acid, it was concluded that the calcium ion exhibited the most promise. When pyrolysed in air with an open gas flame or in a furnace, calcium gluconate monohydrate produces voluminous foam. The foam is of a closed cell structure, densely packed and has no mechanical strength. The cell walls are very thin (5 to 50 nm) and the cells are between 50 µm and 200 µm in size. If the sample is compressed before heating, the resultant foam produced during pyrolysis is less voluminous than that of the loose powder. The BET surface area of the calcium gluconate monohydrate foamed at 300°C for 5 min. is 16.0 m2/g. The foam produced after 5 min heating at 300°C has a thermal conductivity similar to standard polystyrene foam. Adding leached silica to the calcium gluconate monohydrate increases mechanical strength of the foam, but influences the foam volume negatively. The optimum silica level was calculated to be 1:1 gluconate to silica on a mole ratio (11.8% SiO2 by mass). The mechanical strength of the foam can also be increased with the addition of expandable graphite. The graphite has a lesser influence on the foam volume than the silica, but also reduces the foam volume. However, the addition of the expandable graphite gives the sample more .opening. force, as the foam volume of a compressed sample pyrolysed, is similar to that of the heated loose powder. Calcium gluconate monohydrate starts to degrade at 120°C, losing its crystal water and shows a mass loss of 4% at 180°C. The exothermic peak (shown in the DSC/TGA data) associated with the metal catalysed carbon oxidation (afterglow) is observed at 570°C in air. For the calcium gluconate monohydrate the transition from CaCO3 to CaO occurs above 650°C in air. It has been shown that the foaming of polyhydroxylcarboxylic acids is due to the formation of water vapour during degradation. For calcium gluconate monohydrate, foaming starts due to the loss of crystal water and is continued by the loss of hydroxyl groups as water. The bulk of the foaming is due to the second reaction. It has been shown that compounds with crystal waters produce a more voluminous and lower density foam. The foam is an amorphous carbon rich residue. The molecular mass of the carbon residue increases up to a heating temperature of 300°C. This implies that the carbon residue crosslinks during formation, forming a stretchable cell wall for the foam. Compounds with a .free. hydroxyl group at the end of the carbon chain produce a foam of larger volume and lower density. This supports the crosslinking theory. The foam produced when calcium gluconate monohydrate is heated for 5 min at 300°C in air is of very low density . 2.5 kg/m3 based on residual mass. The density of the calcium gluconate monohydrate pyrolysed at 1000°C for 5 min in air yields a CaO with a density of 20 kg/m3 . This implies that the high temperature pyrolysis of calcium gluconate can produce an inorganic oxide of low bulk density and possible high specific surface area. The BET surface area of CaCO3 from the gluconate pyrolysed at 600°C is ~ 12 m2 /g. An intumescent coating containing calcium gluconate monohydrate, leached silica and expandable graphite as a system was prepared and compared to commercial formulations. This gluconate based system was at least as efficient as the commercial formulations when painted on balsa wood planks or aluminium plates. On cardboard sheets it did not perform as well as the commercial systems. More work should be done to overcome the afterglow effect observed with metal- based intumescent systems. The crystal structure of calcium gluconate monohydrate should be determined as to understand the decomposition better. It is unclear whether the decomposition is catalysed inter- or intramolecularly. / Thesis (PhD(Chemical Engineering))--University of Pretoria, 2005. / Chemical Engineering / unrestricted

Poly Brominated Diphenyl Ethers (PBDEs) are known flame retardants with highly persistent and lipophilic in nature. The continued usage of PBDE in various products amplifies the human burden of PBDEs. It is therefore, important to study the potential toxicological and/or biological effects of PBDE exposure in human. In this study we investigated the mode of action of PBDE induced toxicity in human liver by exposing human hepatocarcinoma cells in a time (24-72h) and dose (0-100μM) dependent manner. The highest test dose caused an inhibition in cell viability up to 50% after 72h, whereas lower doses (<50μM) showed slight increase in cell viability. Likewise, higher doses caused significant accumulation of intracellular ROS over time. Further, increase in caspase-3 enzyme levels and DNA fragmentation showed that, lower brominated PBDEs induce liver toxicity through accumulation of toxic metabolites and reactive oxygen species over time leading to caspase-mediated apoptotic cell death.

In the recent years, many research articles focused on endocrine disrupting compounds in the environment. Some of these compounds are listed in a group named brominated flame retardants. However, only few articles investigated endocrine activity of several "new" brominated flame retardants. These chemicals such as 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) or bis(2-ethylhexyl) tetrabromophthalate (TBPH) are newly used due to ban of some previously most produced brominated flame retardant mixes. In this study, we used two recombinant yeast screens to measure estrogenic, androgenic, antiestrognic and antiandrogenic activities of some alternative brominated flame retardants. We also used ligninolytic fungi to investigate biodegradation of these compounds. Our results suggest, that 2,4,6-tribromophenol (TBP) may be a new environmental endocrine disruptor. This substance showed antiestrogenic and antiandrogenic activity in our tests. 1,2-bis(2,4,6- tribromophenoxy)ethane (BTBPE) had certain antagonistic activity too. In the biodegradation experiment, only three compounds showed significant degradation during the test period. No biodegradation have been observed for other compounds. In this study, we applied gas chromatography with mass spectrometry to analyze these "new" flame retardants. Method for gas...

The target of my diploma thesis is evaluation of soil load by polybrominated diphenylethers. This is the soils, which were affected by fire and comparsion with load by soils, which were not affected by fire. In teoretical part available informations about BDE from various sources are processed. Target of practical part is find the optimal method for determination BDE, verification of her yield a determination of reals samples with using this method. In the end this thesis contains measured results, its interpetation in tables, graphes and evaluation of load by individual congeners. Key is comparsion load of soils, which were affected and which were not affected by fire. BDE are released during the fire and we can decide that soils which were caused by fire should be contaminated more, than soils, which were not caused by fire.

No description available.

<p>Accumulating evidence is suggesting that exposure to some environmental contaminants may alter adipogenesis, resulting in accumulation of adipocytes, and often significant weight gain. Thus these types of contaminants are often referred to as obesogens. Many of these contaminants act via the activation (i.e. agonism) of the peroxisome proliferator activated receptor &#947; (PPAR&#947;) nuclear receptor. To date, very few chemicals have been identified as possible PPAR&#61543; ligands. In the thesis, our goal was to determine the PPAR&#947; ligand binding potency and activation of several groups of major semi-volatile organic compounds (SVOCs) that are ubiquitously detected in indoor environments, including flame retardants such as polybrominated diphenyl ethers (PBDEs) and Firemaster 550 (FM550), and other SVOCs such as phthalates, organotins, halogenated phenols and bisphenols. Additional attention was also given to the potential activity of the major metabolites of several of these compounds. Since the primary sink for many of these SVOCs is dust, and dust ingestion has been confirmed as an important pathway for SVOCs accumulation in humans, the potential PPAR&#61543; binding and activation in extracts from environmentally relevant dust samples was also investigated. </p><p> Previous studies have also shown that SVOCs sorbed to organic matrices (e.g., soil and sediment), were only partially bioaccessible (bioavailable), but it was unclear how bioaccessible these compounds are from indoor dust matrices. In addition, bioactivation of SVOCs (via metabolism) could exacerbate their PPAR&#61543; potency. Therefore, to adequately assess the potential risk of PPAR&#947; activation from exposure to SVOC mixtures in house dust, it is essential that one also investigates the bioaccessibility and bioactivation of these chemicals following ingestion. </p><p> In the first research aim of this thesis, the bioaccessibility and bioactivation of several important SVOCs in house dust was investigated. To accomplish this, Tenax beads (TA) encapsulated within a stainless steel insert were used as an infinite adsorption sink to estimate the dynamic absorption of a suite of flame retardants (FRs) commonly detected in indoor dust samples, and from a few polyurethane foam samples for comparison. Experimental results demonstrate that the bioaccessibility and stability of FRs following ingestion varies both by chemical and by matrix. Organophosphate flame retardants (OPFRs) had the highest estimated bioaccessibility (~80%) compared to brominated compounds (e.g. PBDEs), and values generally decreased with increasing Log Kow, with <30% bioaccessibility measured for the most hydrophobic compound tested, BDE209. In addition, the stability of the more labile SVOCs that contained ester groups (e.g. OPFRs and 2-ethylhexyl-tetrabromo-benzoate (TBB)) were examined in a simulated digestive fluid matrix. No significant changes in the OPFR concentrations were observed in this fluid; however, TBB was found to readily hydrolyze to tetrabromobenzoic acid (TBBA) in the intestinal fluid in the presence of lipases. </p><p> In research aims 2 and 3, two commercially available high-throughput bioassays, a fluorescence polarization PPAR&#61543; ligand binding assay (PolarScreenTM PPAR&#947;-competitor assay kit, Invitrogen, Aim 2) and a PPAR&#61543; reporter gene assay (GeneBLAzer PPAR&#947; non-DA Assay, Invitrogen, Aim 3) were used to investigate the binding potency and activation of several groups of SVOCs and dust extracts with human PPAR&#947; LBD; respectively. In the PPAR&#61543; binding assay (Aim 2), most of the tested compounds exhibited dose-dependent binding to PPAR&#947;. Mono(2-ethylhexyl) tetrabromophthalate (TB-MEHP), halogenated bisphenol/phenols, triphenyl phosphate and hydroxylated PBDEs were found to be potent or moderate PPAR&#947; ligands, based on the measured ligand binding dissociation constant (Kd). The most potent compound was 3-OH-BDE47, with an IC50 of 0.24 &#956;M. The extent of halogenation and the position of the hydroxyl group strongly affected binding. Of the dust samples tested, 21 of 24 samples showed significant PPAR&#61543; binding potency at a concentration of 3 mg dust equivalents (DEQ)/mL. In the PPAR&#61543; reporter assay (Aim 3), many SVOCs or their metabolites were either confirmed (based on previous reports) or for the first time were found to be potential PPAR&#947; agonists with various potency and efficacy. We also observed that 15 of 25 dust extracts examined showed an activation percentage more than 8% (calculated activation threshold) of the maximal activation induced by rosiglitazone (positive control). In some cases, activation was as high as 50% of the rosiglitazone activation for the dust extracts with the highest efficacy. Furthermore, the correlation between the reporter assay and the ligand binding assay among the house dust extracts was significant and positive (r = 0.7, p < 0.003), suggesting the binding potency was predicting activation. In research aim 2, the effect of bioactivation on the PPAR&#947; binding potency was also investigated. In vitro bioactivation of house dust extracts incubated with rat and human hepatic S9 fractions was used to investigate the role of in vivo biotransformation on PPAR gamma activity. The result showed that metabolism may lead to an increased binding affinity, as a 3-16% increase in PPAR&#947; binding activity was observed following bioactivation of the dust extracts.</p><p> In research aim 4, an effect-directed analysis (EDA) was used to identify compounds likely contributing to the observed PPAR&#61543; activity among the dust extract. Three dust extracts which showed significant PPAR&#61543; activity with approximately 25, 30, and 50% of the maximal response induced by rosiglitazone at the highest efficacy were fractionated using normal phase high-performance liquid chromatography (NP-HPLC) and each fraction was individually tested for PPAR&#61543; activity. Active fractions were then analyzed using gas-chromatography mass spectrometry (GC-MS) and possible compounds identified. Three dust extracts showed a similar PPAR&#61543; activity distribution among the NP-HPLC fractions. In the most active fractions, fatty acids (FAs) were identified as the most active chemicals. The concentrations of four FAs were measured in the house dust extracts, and the concentrations were found to be highly correlated with the observed PPAR&#61543; activity. These four FAs were also tested for PPAR&#61543; activity and found to be partial PPAR&#61543; agonists, particularly oleic and myristic acid. To tentatively identify sources of FAs, FAs in human/animal hair, dead skin cells, and two brands of cooking oil were analyzed. We found the same FAs in those samples and there concentrations were relatively abundant, ranging from 186 to 14,868 µg/g. Therefore, these results suggest that FAs are likely responsible for the observed PPAR&#61543; activity in indoor dust. Also, this is the first study reporting on the level of FAs in dust samples. The source of these FAs in dust may be either from the cooking or accumulation of human/animal cells in indoor dust.</p><p> In conclusion, this research demonstrates that many SVOCs ubiqutiously detected in house dust, and/or their metabolites, can be weak or moderate PPAR&#61543; ligands. In addition, chemical mixtures in house dust can effectively bind to and activate PPAR&#61543;. However, our results suggest FAs are probably responsible for these observations, and likely outcompeting the synthetic environmental contaminants present in the dust extract. Furthermore, bioactivation of contaminants present in house dust can potentially increase their affinity for PPAR&#61543;. And lastly, the bioaccessibility and stability of SVOCs in house dust after ingestion are likely to modulate the PPAR&#61543; activity in the environmental mixtures and should be considered in future risk assessments.</p> / Dissertation

Rapid economic development has occurred during the past few decades in China with the Yangtze River Delta (YRD) area as one of the most progressive areas. The urbanization, industrialization, agricultural and aquaculture activities result in extensive production and application of chemicals. Organohalogen contaminants (OHCs) have been widely used as i.e. pesticides, flame retardants and plasticizers. They are persistent, bioaccumulative and pose a potential threat to ecosystem and human health. However, limited research has been conducted in the YRD with respect to chemicals environmental exposure. The main objective of this thesis is to investigate the contamination level, distribution pattern and sources of OHCs in the YRD. Wildlife from different habitats are used to indicate the environmental pollution situation, and evaluate selected matrices for use in long term biomonitoring to determine the environmental stress the contamination may cause. In addition, a method is developed for dicofol analysis. Moreover, a specific effort is made to introduce statistic power analysis to assist in optimal sampling design. The thesis results show extensive contamination of OHCs in wildlife in the YRD. The occurrences of high concentrations of chlorinated paraffins (CPs) are reported in wildlife, in particular in terrestrial species, (i.e. short-tailed mamushi snake and peregrine falcon). Impurities and byproducts of pentachlorophenol products, i.e. polychlorinated diphenyl ethers (PCDEs) and hydroxylated polychlorinated diphenyl ethers (OH-PCDEs) are identified and reported for the first time in eggs from black-crowned night heron and whiskered tern. High concentrations of octachlorodibenzo-p-dioxin (OCDD) are determined in these samples. The toxic equivalents (TEQs) of polychlorinated dibenzo-p-dioxin (PCDDs) and polychlorinated dibenzofurans (PCDFs) are at mean levels of 300 and 520 pg TEQ g-1lw (WHO2005 TEQ) in eggs from the two bird species, respectively. This is two orders of magnitude higher than European Union (EU) regulation limit in chicken eggs. Also, a novel pattern of polychlorinated biphenyls (PCBs) with octa- to decaCBs, contributing to as much as 20% of total PCBs therein, are reported in birds. The legacy POPs shows a common characteristic with relatively high level of organochlorine pesticides (i.e. DDT, hexacyclohexanes (HCHs) and Mirex), indicating historic applications. In contrast, rather low concentrations are shown of industrial chemicals such as PCBs and polybrominated diphenyl ethers (PBDEs). A refined and improved analytical method is developed to separate dicofol from its major decomposition compound, 4,4’-dichlorobenzophenone. Hence dicofol is possible to assess as such. Statistic power analysis demonstrates that sampling of sedentary species should be consistently spread over a larger area to monitor temporal trends of contaminants in a robust manner. The results presented in this thesis show high CPs and OCDD concentrations in wildlife. The levels and patterns of OHCs in YRD differ from other well studied areas of the world. This is likely due to the extensive production and use of chemicals in the YRD. The results strongly signal the need of research biomonitoring programs that meet the current situation of the YRD. Such programs will contribute to the management of chemicals and environment in YRD, with the potential to grow into the human health sector, and to expand to China as a whole. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Manuscript. Paper 5: Submitted. Paper 6: Manuscript.</p><p> </p>

Os retardantes de chama bromados são substâncias utilizadas em bens de consumo para aumentar sua resistência ao fogo e/ou altas temperaturas. Para este fim os Éteres Difenílicos Polibromados (PBDEs do inglês polybrominated diphenyl ether) representam a classe mais utilizada tendo em vista sua eficiência no controle da propagação da chama e baixo custo. Estes compostos são considerados persistentes, bioacumuláveis, podem ser transportados para longas distâncias e apresentam toxicidade podendo causar desregulação endócrina, entretanto os mecanismos de toxicidade ainda não foram bem estabelecidos. Desta forma, o presente projeto utilizou linhagens celulares de Hepatoblastoma Humano (HepG2), HeLa, Hepatócitos e linfócitos humanos a fim de elucidar seus mecanismos de toxicidade. Os resultados significativos demonstram a capacidade destes compostos em induzir dano primário no DNA (0,5 ?mol/L para o BDE-153 e 5 ?mol/L para o BDE-100) monitorado pelo teste do cometa, que não foi reparado após 24 horas de exposição. No entanto, não se observou um aumento de micronúcleos em HepG2 e linfócitos após exposição aos congêneres (0,1 - 25 ?mol/L) nem mesmo mutagenicidade no ensaio de Salmonella typhimurium. Contudo, os compostos apresentam capacidade de diminuir a redução do brometo de 3-(4,5 dimetiltiazol-2il)-2,5 difenil tetrazólio (MTT), proliferação e interferem no ciclo celular nos cultivos celulares avaliados. Estes efeitos de citotoxicidade estão relacionados com a disfunção mitocondrial, uma vez que ambos PBDEs geram dissipação do potencial de membrana mitocondrial, formação e acúmulo de espécies reativas, culminando em morte celular apoptótica, demonstrada pela manutenção da fosfatidil serina na face externa da membrana celular, pela condensação e fragmentação nuclear, presença de fatores pró-apoptóticos no citosol da célula, tais como citocromo C e AIF além da ativação de caspases 3 e 9. Estes dados corroboram com o fato de não ter liberação de lactato desidrogenase intracelular, excluindo a morte celular por necrose. E por fim, foi possível observar que a exposição aos compostos ativa o processo autofágico, a princípio como um mecanismo de citoproteção observado pela conversão de LC3I em LC3II e acúmulo de p62 (marcadores autofágicos) além de marcações imunicitoquímicas para LC3II e co-localização de lisossomos no padrão pontuado, indicanto acúmulos da proteína LC3 e lisossomos, formando os autofagossomos. Em conjunto nossos resultados apresentam a capacidade de induzir instabilidade genômica e citotoxicidade desta classe de compostos, reforçando a idéia de que os PBDEs representam risco à população exposta / The brominated flame retardants are substances used in consumer goods to increase its fire resistance and/or high temperatures. Due to, the polybrominated diphenyl ethers (Polybrominated diphenyl ether) are the most commonly used class in view of its efficiency in controlling the spread of flame and low cost. These compounds are considered persistent, bioaccumulative, can be transported over long distances and have toxicity. However the toxic mechanisms of action have not been well established. Thus, this project held cytotoxic, genotoxic and mutagenic assays in HepG2, HeLa, hepatocytes and human lymphocytes cells in order to elucidate the mechanisms of toxicity. The results demonstrate the ability of these compounds to induce primary DNA damage (0.5 ?M for BDE-153 and 5 ?M for BDE-100) monitored by the comet assay, it was not repaired after 24 hours of exposure. However, there was not observed nether increase in micronuclei in HepG2 cells and lymphocytes after exposure to the congeners (0.1 - 25 ?M) even in the Salmonella typhimurium mutagenicity assay. However, the compounds show the ability to reduce MTT reduction, proliferation, and interfere with cell cycle evaluated in cell cultures. These cytotoxic effects are related to mitochondrial dysfunction, since both PBDE generate dissipation of the mitochondrial membrane potential, accumulation of reactive oxygen species, resulting in apoptotic cell death, demonstrated by the maintenance of serine phosphatidyl on the external surface of the cell membrane, by condensation and nuclear fragmentation, the presence of pro-apoptotic factors in the cytosol of the cell, such as cytochrome c and AIF plus activating caspase 3 and 9. These data corroborate the fact of not having to intracellular lactate dehydrogenase release, excluding death cell necrosis. Finally, it was observed that exposure to the active compounds the autophagic process, at first as a cytoprotective mechanism observed by LC3I conversion in LC3II and accumulation of p62 (autophagic markers) plus imunicitoquímicas markings for LC3II and co-location lysosomes in dotted pattern, indicanto accumulations of LC3 protein and lysosomes, forming autophagosomes. Together our results show the ability to induce genomic instability and cytotoxicity of this class of compounds, reinforcing the idea that PBDEs pose a risk to the exposed population

Fish are particularly vulnerable to the exposure of anthropogenic pollutants, with a vast array of endocrine disrupting chemicals (EDCs) introduced into the aquatic environment via sewage discharge, waste disposal and land runoff. Brominated flame retardants (BFRs) are halogenated flame retardants that are used to effectively inhibit the flammability of various materials including plastic products, electrical appliances, construction materials and textiles. BFRs are ubiquitous environmental contaminants and are known to disrupt thyroid hormone (TH) homeostasis in several vertebrate species, including fish. Given the vital role of THs in a wide range of developmental processes and physiological functions, assessing and identifying thyroid disrupting chemicals is crucial for safe guarding the long-term health of humans and wildlife. In fish the molecular mechanisms underlying TH disruption by BFRs and the effects on TH-sensitive tissues during early life stages remains unclear. This has been limited by the lack of fundamental knowledge on the TH system of fish and the difficulties associated with examining transcriptional changes in discrete embryonic-larval tissues. Here I have established the expression profiles of a suite of genes in the hypothalamic-pituitary-thyroid (HPT) axis of zebrafish (Danio rerio) during embryonic-larval stages and their regulation by the biologically active TH (3, 5, 3′- tri-iodothyronine; T3). Using molecular tools (whole mount is situ hybridisation and RT-PCR), I demonstrate that a number of genes display spatial and temporal expression profiles during embryo/larval development, and their regulation by T3 was tissue- and developmental stage-specific. I subsequently demonstrated that TBBPA and BDE-47, two important BFR compounds, disrupted TH homeostasis at multiple levels of the HPT axis of zebrafish embryo-larvae after short sub-acute exposures. These compounds altered the expression of genes associated with TH conjugation and clearance, thyroid follicle development and TH transport. In addition, we suggest that TH target genes in the brain, liver, pronephric ducts and craniofacial tissues of zebrafish embryo-larvae may be particularly vulnerable to TBBPA and BDE-47 exposure. It has been proposed that environmental pollutants can disrupt TH signalling in wildlife by disrupting the activity of thyroid receptors (TRs), ligand-binding transcription factors, which mediate the genomic actions of THs. The ability of BFRs to disrupt fish TRs has not yet been examined. Here I developed an in vitro reporter gene transcriptional assay for zebrafish thyroid hormone receptors (zfTRα and zfTRβ) in human embryonic kidney cells and investigated their interactions with several BFR compounds. The assays were optimised and validated using the natural TR agonist T3 in cells transiently transfected with two reporter vector constructs, pGL4.24-PAL and pGL4.24-DR4. None of the six brominated flame retardants tested, namely, tetrabromobisphenol A (TBBPA), hexabromocyclododecane (HBCD), 2,2′,4,4′-tetra-bromodiphenyl ether (BDE-47), 2,2′,4,4′,6-penta-bromodiphenyl ether (BDE-100), 2,2′,3,4,4′,5′,6-hepta-bromodiphenyl ether (BDE-183) and deca-bromodiphenyl ether (BDE-209) had an agonistic effect on zfTRα and zfTRβ activity. These results are consistent with our previous finding which suggests that altered TH homeostasis may be a result of increased metabolism and excretion of THs and/or changes in the production of TH by the thyroid follicles. In conclusion, this investigative work aids the understanding of fundamental TH processes in fish, such as gene expression and regulation, and increases our understanding of the mechanisms and potential targets of BFRs in fish.

<p>This thesis examines developmental neurotoxic effects of polybrominated diphenyl ethers (PBDEs), PBDE 99, PBDE 153, and the fully brominated PBDE 209, after exposure during the newborn period in rodents.</p><p>Our environment contains vast numbers of contaminants, including the flame retardants, PBDEs. The PBDEs are widely found in the environment and are increasing in human milk. Individuals can be exposed to PBDEs during their whole lifetime, and especially during the lactation period. The neonatal period, coinciding with the lactation period, is characterized in many mammalian species by rapid growth and development of the immature brain. It has been shown that numerous toxicants can induce permanent disorders in brain function when administered to the neonatal mouse during the brain growth spurt (BGS). In mice and rats this period is postnatal, spanning over the first 3-4 weeks of life, while in humans, BGS begins during the third trimester of pregnancy and continues throughout the first two years of life.</p><p>The present studies identified a defined critical period during BGS in mice when the brain is vulnerable to insults of low doses of PBDEs and that it is the presence of PBDEs or their metabolites in the brain during this critical period that is crucial to evoking neurotoxic effects. The effects observed are permanent altered spontaneous behavior, reduced habituation, deficits in learning and memory, and disturbances in the cholinergic system. These effects worsen with age.</p><p>The ability of PBDEs to induce neurotoxic effects does not appear to be gender-, strain- or species-specific, because the neurotoxic effects are induced in rats and male and female mice of different strains.</p><p>The developmental neurotoxic effects of PBDEs are similar to those observed for polychlorinated biphenyls (PCBs) and possible interactive effects of PBDEs and other environmental contaminants are therefore of concern.</p>