Existem muitos estudos sobre a ocorrência de poluentes orgânicos persistentes (POPs) no ambiente marinho utilizando bioindicadores como os tubarões. Entretanto, no Brasil, ainda há carência de dados de POPs nesses organismos. O objetivo desta pesquisa foi investigar a ocorrência e o comportamento dos PCBs, pesticidas organoclorados e PBDEs no ambiente marinho, a partir da utilização dos tubarões como indicadores. Musculatura e fígado de vinte tubarões-azul (Prionace glauca) foram coletados em agostosetembro de 2008. Os PCBs foram os poluentes predominantes, presentes em 80% das amostras, com concentrações variando de <n.d. a 427,28 ng.g-1 de peso úmido. Os diclorodifeniletanos apresentaram concentrações variando de 0,43 a 202,42 ng.g-1 de peso úmido, no qual o 4,4´-DDE foi o composto mais significativo, com 77,6% de contribuição para os DDTs totais. As concentrações no fígado foram 1-2 ordens de grandeza mais elevadas, em relação às de musculatura. Houve um padrão de distribuição dos poluentes com níveis equivalentes entre indivíduos imaturos. Os machos maduros apresentaram concentrações de POPs sensivelmente maiores que as fêmeas maduras, indicando a transferência dos POPs para os filhotes. Os resultados demonstraram a ampla distribuição desses poluentes no ambiente marinho. / There are many studies about the occurrence of persistent organic pollutants (POPs) in the marine environment using sharks as bioindicators. However, there is still a lack of data of POPs in those organisms in Brazil. The goal of this research was to investigate the occurrence and behavior of PCBs, organochlorine pesticides and PBDEs in the marine environment, using sharks as indicators. Muscle and liver of twenty blue-sharks (Prionace glauca) were collected in august-september 2008. The PCBs were the predominant pollutants and being present in 80% of samples, with concentrations ranging from <n.d. to 427.28 ng.g-1 wet weight. The dichlorodiphenylethanes present concentrations ranging from 0.43 to 202.42 ng.g-1 wet weight, where the 4,4´-DDE was the most significative compound, with contributions of 77,6% of the total DDTs. The concentrations in the liver were 1-2 orders of magnitude higher than in the muscle. There was a distribution pattern of the pollutants, with equivalent levels among the immature specimens. The concentration of POP was significantly higher in the mature males and relatively lower in the mature female, showing the maternal transference of POPs to the pups. The results have demonstrated a wide distribution of these pollutants in the marine environment.

Os PCBs, do inglês Polychlorinated Biphenyls (bifenilas policloradas), é o nome genérico dado à classe de compostos organoclorados resultante da reação do grupo bifenila com cloro anidro na presença de catalisador. São tóxicos, persistentes, bioacumulativos e representam o risco de provocar efeitos nocivos à saúde humana e ao meio ambiente. Grandes quantidades de PCBs foram produzidos em vários países entre 1927 e 1977. Nos Estados Unidos a proibição ocorreu em 1977. Utilizados como fluidos dielétricos em transformadores elétricos e capacitores em todo o mundo, comercialmente conhecidos como Ascarel, dentre outras denominações, tais como Aroclor, Pyralene, Clorophen, Inerteen, Asbestol e Kneclor. Devido à alta toxicidade, a produção e comercialização dos PCBs foram proibidas no mundo todo a partir de 1980. No Brasil, transformadores que tiveram o óleo mineral isolante, contaminado por PCBs, estando em uso ou em armazenamento, segundo os critérios da Norma ABNT NBR 13882, a destinação final do óleo isolante deverá ser feita por incineração e ou descontaminação a valores inferiores a 50mg/kg. Neste trabalho realizado no Instituto de Química de São Carlos - Universidade de São Paulo, desenvolveu-se um procedimento para a descontaminação de óleo contaminado com valor conhecido acima de 50mg/kg, por percolação em coluna contendo espuma de poliuretano derivada de óleo de mamona, produzida pelo Laboratório de Química Analítica e Tecnologia de Polímeros (GQATP), obtendo-se uma redução de 55% dos níveis de PCBs em óleo contaminado. As espumas foram funcionalizadas com tiodiglicol e polissulfeto de amônio, obtendo-se respectivamente 24% e 11% de redução dos níveis de PCBs em óleo contaminado. Observou-se que a espuma de poliuretano produzida pelo GQATP, funciona como um adsorvente eficaz na remoção de PCBs, e que a utilização de n-hexano na dessorção da espuma, permite remover praticamente todos os PCBs adsorvidos. Portanto, esses tipos de espumas podem servir como adsorventes altamente eficazes na remoção dos PCBs presentes nos óleos minerais isolantes e, portanto, contribuir significativamente para a proteção do meio ambiente. / PCBs, (polychlorinated biphenyls), is the generic name given to the class of organochlorine compounds resulting from the reaction of the biphenyl group with anhydrous chlorine in the presence of catalyst. They are toxic, persistent, bioaccumulative and pose the risk of causing harm to human health and the environment. Large quantities of PCBs were produced in several countries between 1927 and 1977. In the United States the prohibition occurred in 1977. Used as dielectric fluids in electrical transformers and capacitors in the world, commercially known as Ascarel, among other names such as Aroclor, Pyralene, Clorophen, Inerteen, and Asbestol Kneclor. Due to high toxicity, production and marketing of PCBs have been banned worldwide since 1980. In Brazil, transformers that had insulating mineral oil, contaminated with PCBs, while in use or in storage, according to the criteria of the Standard NBR 13,882, the final destination of insulating oil should be by incineration or decontamination and the values below 50mg/kg. In a previous work carried out at the Chemistry Institute of Sao Carlos - University of Sao Paulo, a procedure was developed for the decontamination of oil contaminated with known value above 50 mg / kg of percolation column containing polyurethane foam derived from castor oil produced Laboratory of Analytical Chemistry and Technology of Polymers (GQATP), resulting in a 55% reduction in the levels of PCBs in contaminated oil. Foams were functionalized with thiodiglycol and Ammonium polysulfide, yielding respectively 24% and 11% reduction in the levels of PCBs in contaminated oil. It was observed that the polyurethane foam produced by GQATP function as an effective adsorbent for removal of PCBs, and that the use of n-hexane desorption of the foam allows to remove virtually all PCBs adsorbed. So these types of foam can serve as highly efficient adsorbents for the removal of PCBs present in the insulating mineral oil, and thus contribute significantly to environmental protection.

Os PCBs, do inglês Polychlorinated Biphenyls (bifenilas policloradas), é o nome genérico dado à classe de compostos organoclorados resultante da reação do grupo bifenila com cloro anidro na presença de catalisador. São tóxicos, persistentes, bioacumulativos e representam o risco de provocar efeitos nocivos à saúde humana e ao meio ambiente. Grandes quantidades de PCBs foram produzidos em vários países entre 1927 e 1977. Nos Estados Unidos a proibição ocorreu em 1977. Utilizados como fluidos dielétricos em transformadores elétricos e capacitores em todo o mundo, comercialmente conhecidos como Ascarel, dentre outras denominações, tais como Aroclor, Pyralene, Clorophen, Inerteen, Asbestol e Kneclor. Devido à alta toxicidade, a produção e comercialização dos PCBs foram proibidas no mundo todo a partir de 1980. No Brasil, transformadores que tiveram o óleo mineral isolante, contaminado por PCBs, estando em uso ou em armazenamento, segundo os critérios da Norma ABNT NBR 13882, a destinação final do óleo isolante deverá ser feita por incineração e ou descontaminação a valores inferiores a 50mg/kg. Neste trabalho realizado no Instituto de Química de São Carlos - Universidade de São Paulo, desenvolveu-se um procedimento para a descontaminação de óleo contaminado com valor conhecido acima de 50mg/kg, por percolação em coluna contendo espuma de poliuretano derivada de óleo de mamona, produzida pelo Laboratório de Química Analítica e Tecnologia de Polímeros (GQATP), obtendo-se uma redução de 55% dos níveis de PCBs em óleo contaminado. As espumas foram funcionalizadas com tiodiglicol e polissulfeto de amônio, obtendo-se respectivamente 24% e 11% de redução dos níveis de PCBs em óleo contaminado. Observou-se que a espuma de poliuretano produzida pelo GQATP, funciona como um adsorvente eficaz na remoção de PCBs, e que a utilização de n-hexano na dessorção da espuma, permite remover praticamente todos os PCBs adsorvidos. Portanto, esses tipos de espumas podem servir como adsorventes altamente eficazes na remoção dos PCBs presentes nos óleos minerais isolantes e, portanto, contribuir significativamente para a proteção do meio ambiente. / PCBs, (polychlorinated biphenyls), is the generic name given to the class of organochlorine compounds resulting from the reaction of the biphenyl group with anhydrous chlorine in the presence of catalyst. They are toxic, persistent, bioaccumulative and pose the risk of causing harm to human health and the environment. Large quantities of PCBs were produced in several countries between 1927 and 1977. In the United States the prohibition occurred in 1977. Used as dielectric fluids in electrical transformers and capacitors in the world, commercially known as Ascarel, among other names such as Aroclor, Pyralene, Clorophen, Inerteen, and Asbestol Kneclor. Due to high toxicity, production and marketing of PCBs have been banned worldwide since 1980. In Brazil, transformers that had insulating mineral oil, contaminated with PCBs, while in use or in storage, according to the criteria of the Standard NBR 13,882, the final destination of insulating oil should be by incineration or decontamination and the values below 50mg/kg. In a previous work carried out at the Chemistry Institute of Sao Carlos - University of Sao Paulo, a procedure was developed for the decontamination of oil contaminated with known value above 50 mg / kg of percolation column containing polyurethane foam derived from castor oil produced Laboratory of Analytical Chemistry and Technology of Polymers (GQATP), resulting in a 55% reduction in the levels of PCBs in contaminated oil. Foams were functionalized with thiodiglycol and Ammonium polysulfide, yielding respectively 24% and 11% reduction in the levels of PCBs in contaminated oil. It was observed that the polyurethane foam produced by GQATP function as an effective adsorbent for removal of PCBs, and that the use of n-hexane desorption of the foam allows to remove virtually all PCBs adsorbed. So these types of foam can serve as highly efficient adsorbents for the removal of PCBs present in the insulating mineral oil, and thus contribute significantly to environmental protection.

Polychlorinated biphenyls (PCBs) and their metabolic derivatives are ubiquitous environmental contaminants. These compounds are of concern because of their persistence and bioaccumulation in nature. PCBs and the hydroxylated metabolites have shown endocrine-disrupting activity. A method of detection in surface water samples is important to identify and quantify the environmental contamination. In this research we have attempted to develop a method of detection. Six representative polychloromethoxybiphenyls (PCMBs) were prepared. The corresponding polychlorobiphenylols, hydroxylated PCB metabolites (OH-PCBs), were prepared from the PCMBs. A method coupling solid phase extraction with liquid chromatography, on-line electrospray ionization, and mass spectrometry (SPE-LC/ESI/MS) was developed for detection of the OH-PCBs in distilled and surface water samples.

Polychlorinated biphenyls (PCBs) are toxic and persistent chemicals that have been largely dispersed into the environment. The biological and abiotic transformations of PCBs often generate hydroxylated derivatives, which have been detected in a variety of environmental samples, including animal tissues and feces, water, and sediments. Because of their toxicity and widespread dispersion in the environment, hydroxylated PCBs (OH-PCBs) are today increasingly considered as a new class of environmental contaminants. Although PCBs are known to be susceptible to microbial degradation under both aerobic and anaerobic conditions, bacterial degradation of OH-PCBs has received little attention. The overall objective of this study is therefore to evaluate the transformation of mono-hydroxylated PCBs by the well characterized aerobic PCB-degrading bacterium, Burkholderia xenovorans LB400. In order to achieve our overall objective, a series of model mono-hydroxylated PCBs have been selected and they are used to determine the toxicity of hydroxylated congeners toward the bacterium B. xenovorans LB400. The biodegradation kinetics and metabolic pathways of the selected OH-PCBs by B. xenovorans LB400 are then characterized using GC/MS. To understand further the molecular basis of the metabolism of OH-PCBs by B. xenovorans LB400, gene expression analyses are conducted using reverse-transcription real-time (quantitative) polymerase chain reaction (RT-qPCR) and microarray technology. More formally, the specific aims of the proposed research are stated as follows: (1) To evaluate the toxicity of selected mono-hydroxylated derivatives of lesser-chlorinated PCBs toward the bacterium B. xenovorans LB400. (2) To assess the degradation of the selected OH-PCBs by B. xenovorans LB400. (3) To gain further understanding of the molecular bases of the metabolism of the selected OH-PCBs by B. xenovorans LB400. Three hydroxylated derivatives of 4-chlorobiphenyl and 2,5-dichlorobiphenyl, including 2'-hydroxy-, 3'-hydroxy-, and 4'-hydroxy- congeners, were significantly transformed by Burkholderia xenovorans LB400 when the bacterium was growing on biphenyl (biphenyl pathway-inducing conditions). On the contrary, only 2'-OH-4-chlorobiphenyl and 2'-OH-2,5-dichlorobiphenyl were transformed by the bacterium growing on succinate (conditions non-inductive of the biphenyl pathway). Gene expression analyses showed that only exposure to 2'-OH-4-chlorobiphenyl and 2'-OH-2,5-dichlorobiphneyl resulted in induction of key genes of the biphenyl pathway, when cells grown on succinate. These observations suggest that 2'OH-PCBs were capable of inducing the genes of biphenyl pathway. These results provide the first evidence that bacteria are able to cometabolize PCB derivatives hydroxylated on the non-chlorinated ring. Genome-wide transcriptional analyses using microarrays showed that 134 genes were differentially expressed in cells exposed to biphenyl, 2,5-dichlorobiphenyl, and 2'-OH-2,5-dichlorobiphneyl as compared to non-exposed cells. A significant proportion of differentially expressed genes were simultaneously expressed or down regulated by exposure to the three target compounds i.e., biphenyl, 2,5-DCB, and 2'-OH-2,5-DCB, which suggests that these structurally similar compounds induce similar transcriptional response of B.xenovorans LB400. Results of this study may have important implications for the natural attenuation of PCBs and fate of OH-PCBs in the environment. The recalcitrance to biodegradation and the high toxicity of some OH-PCBs may provide a partial explanation for the persistence of PCBs in the environment. / Civil Engineering

Lake Vättern has been contaminated with high levels of polychlorinated biphenyls (PCBs) for decades, which could be due to the release of wastes from industries and urban communities surrounding the water system. This has especially had a negative effect on fatty fishes, which could accumulate large amounts of persistent organic pollutants (POPs) and thereby also become a source of environmental toxicants to humans through consumption. Most PCB analysis only quantify a handful of congeners, the so called indicator-PCBs (I-PCBs), but this might leave out important information. In this study, an existing analytical method was improved by supplementing with additional congeners to detect a larger set of PCB congeners in Arctic char (Salvelinus salvelinus) and European whitefish (Coregonus acronius) caught from Lake Vättern, Sweden. New pre-packed multilayer silica columns from CAPE technologies were tested and used to pretreat the fish samples prior to analysis with a Gas Chromatograph coupled to low-resolution Mass Spectrometer using Atmospheric Pressure Ionization (API GC/MS). It was found that modifications of the clean up method for PCBs were necessary, such as lowering the amount of hexane in the washing step and combining the two eluent fractions. The Arctic char and the European whitefish showed a fat content of 0.18% and 0.74%, respectively. Concentrations of detected congeners ranged from 0.5 to 1470 pg g-1 fresh weight (fw) in Arctic char and varied between 1.2 to 6550 pg g-1 in European whitefish. For Arctic char and European whitefish, the WHO2005-TEQ values were 0.4 pg g-1 fw and 0.6 pg g-1 fw, respectively. The greatest total PCB concentration of 25900 pg g-1 was measured in European whitefish. The total concentration of I-PCBs (#28, 52, 101, 138, 153, 180) was 3710 pg g-1 for the Arctic char and 13900e pg g-1 for the European whitefish. All obtained results were lower than those reported from other studies. Constructed congener profiles show that the two species have similar ratios of PCB #138 and #153. Differences are observed of PCBs with a higher chlorination grade, probably due to differences in migration patterns, habitats of the lake, diets, metabolism or bioaccumulation.

Polychlorinated biphenyls (PCBs) are nongenotoxic hepatic tumor promoters. PCBs have been shown to cause oxidative stress, but the exact mechanism by which PCBs exert their tumor promoting activity is not clear. In our study, PCB-153, a non-coplanar congener, caused a transient increase in hepatic NF-B DNA binding activity and cell proliferation, while PCB-77, a coplanar congener, showed no effect. Our second study using a mouse model that was deficient in the p50 subunit of NF-kB (p50-/-) showed that NF-kB contributes to the changes in hepatocyte proliferation and apoptosis in response to PCB-153 treatment: a single dose of PCB-153 increased hepatic NF-B activity and cell proliferation in wild type mice, but not in the p50-/- mice; longer-term treatment with PCB-153 increased cell proliferation in p50-/- mice, but this increase was less than that in the wild type. In addition, p50-/- livers had more apoptosis than in the wild type, and PCB-153 inhibited apoptosis in the p50-/- livers. p50-/- livers had less cyclin D1 protein than the wild type, but that the mRNA levels were same. Bcl-xL protein was not changed by PCB-153, and wild type and p50-/- mice had the same level of Bcl-xL protein. In the third study, PCB-77 caused an increase in hepatic NF-kB DNA binding activity and cell proliferation during the promotion stage, and this increase was blocked by dietary supplementation of vitamin E, but the number and volume of placental glutathione S-transferase (PGST)-positive foci were slightly, though insignificantly, increased in the same animals. The apparent conflict could be due to different effect in different cells: high level vitamin E significantly inhibited PCB-77-induced cell proliferation in normal hepatocytes, while this inhibitory effect was much less in the PGST-positive hepatocytes. In conclusion, our studies show that a non-coplanar PCB can cause an increase in hepatic NF-kB DNA binding activity in rats and mice, and this increase contributes to the change in cell proliferation and apoptosis. Dietary vitamin E supplementation did not show protective effect on the formation of altered hepatic foci that were promoted by PCBs, although vitamin E supplementation decreased PCBs-induced hepatic NF-kB activation and cell proliferation.

Master of Science / Department of Statistics / Wei-Wen Hsu / Polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE) are endocrine disrupting chemicals which can imbalance the hormonal system in the human body and lead to deleterious diseases such as diabetes, irregular menstrual cycles, endometriosis, and breast cancer. These chemicals as environmental exposures still exist in the environment and food chains and can be accumulated in human fatty tissues for many years. These chemicals can also be passed from mothers to their children through placental transfer or breastfeeding; therefore, their offspring may be at increased risk of adverse health outcomes from these inherited chemicals. However, it is still unclear how the parental association with offspring health outcomes and the inter-generational phenotypic inheritance could be affected by these chemical compounds. In this study, we mainly focus on how PCBs and DDE can affect the inheritance of Body Mass Index (BMI) across generations, as BMI is the primary health outcome (or phenotype) linked to diabetes. We propose a biometrical inheritance model to investigate the effects of PCBs and DDE on the heritability of BMI over two generations. Technically, a linear mixed effects model is developed based on the decomposition of phenotypic variance and assuming the variance of the environmental effect depends on parental exposures. The proposed model is evaluated extensively by simulations and then is applied to Michigan Fisheater Cohort data for answering the research question of interest.

Concentrations of PCB congeners were measured in indoor/outdoor pairs of 120 residences in two communities. More than 270 passive samplers equipped with polyurethane foam disks (PAS-PUF) were deployed and collected in the urban/industrial community of East Chicago, Indiana and rural Columbus Junction, Iowa. The sampling protocol included transport and storage of pre-cleaned and exposed PUF disks to and from the laboratory in Iowa City. The potential exposure to PCBs during transport and shipping was found to contribute no more than 10% of the PCBs measured in samples, although the sealed polyethylene bags were insufficient protection from ambient air over longer time periods. The samples were extracted and analyzed for the full suite of 209 polychlorinated biphenyls (PCBs) and are reported as a set of 158 individual or coeluting compounds. The quality control measures included laboratory and travel blanks, injection of surrogate standards in every sample, and analysis of certified PCBs in standard reference materials. Although we hypothesized that homes in East Chicago would have higher PCB concentrations than in rural Columbus Junction, this was not the case: the communities had no significant difference in either indoor or outdoor PCB concentrations (0.62 ± 0.65 ng m-3 and 1.3 ± 1.6 ng m-3 for outdoor air respectively and 1.9 ± 1.4 ng m-3 and 1.9 ± 4.4 ng m-3 for indoor air respectively). In both communities, indoor air was higher in concentration, with indoor/outdoor ratios averaging 3. The samples from the two communities do exhibit statistically different congener distributions, however, with higher molecular weight congeners more enriched in East Chicago.

Environmental contamination is a public health concern. In particular persistent organic pollutants like Polychlorinated Biphenyls (PCBs) have been associated with multiple chronic inflammatory diseases, including non-alcoholic fatty liver disease (NAFLD). NAFLD prevalence has steadily increased and is expected to continue to rise with an estimated 25% of the world’s population and 80-100 million people affected in the United States alone. Importantly, the liver is the primary site for endobiotic and xenobiotic metabolism, hence its proper function is critical for the body’s response to innate and extrinsic molecules. One way to combat the deleterious effects of PCB toxicity and fatty liver disease is by increasing consumption of beverages and foods that contain beneficial bioactive nutrients, like dietary polyphenols. However, the biological properties of these dietary compounds are subject to their bioavailability which is directly dependent on the activity of the liver. The first aim of this dissertation was to test the hypothesis that in the presence of a compromised liver, PCB-126 toxicity is altered. Indeed, hepatic and systemic PCB-126 toxicity was exacerbated in this severe liver injury mouse model with an observed increase in hepatic inflammation, systemic inflammation, and early markers of endothelial cell dysfunction. Interestingly, we also observed an increase in the novel gut-liver axis derived cardiovascular disease (CVD) marker trimethylamine-N-oxide (TMAO). Taken altogether, aim 1 proved that a compromised liver can alter PCB toxicity, with implications of the gut microbiota in disease pathology. In aim 2 we investigated whether GTE can protect against MCD-induced hepatic toxicity and development of NAFLD. Results indicated that MCD mice exhibited severe liver injury and gut dysbiosis and unexpectedly, GTE had no protective effects. Interestingly MCD mice displayed differential epigallocatechin-3-gallate (EGCG) metabolism at the hepatic and gut microbiota level, which may alter polyphenol bioavailability and therapeutic potential. Overall, the results provide insight into how a dysfunctional liver and gut dysbiosis can alter polyphenol metabolism, possibly reducing its therapeutic efficiency. In aim 3 we sought to determine potential protective effects of a prebiotic in this mouse model. MCD-fed mice were exposed to PCB-126 with or without inulin supplementation. Although findings from this study are preliminary, our evidence indicates that inulin restores body weight and body composition in this MCD+PCB mouse model and alters the expression of Cyp1a1 in PCB exposed mice, suggesting that inulin’s protective effects may be a result of its ability to interact with the AhR pathway. However further analysis will need to be done to examine the effects of inulin on hepatic, systemic, and gut microbiota endpoints. Overall the data contained in this dissertation suggests that in the presence of a compromised liver both pollutant toxicity and nutrient metabolism are altered, with implications of the gut-microbiota in disease risk. These findings suggest that individuals with end stage liver injury may be more susceptible to pollutant-induced toxicity and nutritional intervention may be unsuccessful at mitigating disease risk.