| 1. |
- Dahlberg, Anna-Karin, 1985-
(författare)
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Environmentally relevant chemical disruptors of oxidative phosphorylation in Baltic Sea biota : Exposure and toxic potentials
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis focuses on toxicity and occurrence of hydroxylated polybrominated diphenyl ethers (OH-PBDEs) in Baltic Sea biota. The aims were to assess OH-PBDEs potency for disruption of oxidative phosphorylation (OXPHOS) and determine their and related compounds exposure in Baltic blue mussel, herring and long-tailed duck. A method for analysis of OH-PBDEs in herring and long-tailed duck plasma was also evaluated.Relevant OH-PBDEs were tested in vitro for OXPHOS disruption, using a classic rat mitochondrial respiration assay and a cell mitochondrial membrane potential assay. All compounds were found to disrupt OXPHOS either by protonophoric uncoupling and/or via inhibition of the electron transport chain. 6-OH-BDE47 and 6-OH-BDE85, were identified as particularly potent OXPHOS disruptors. Strong synergism was observed when OH-PBDEs were tested as a mixture corresponding to what is present in Baltic blue mussels.Baltic blue mussel is main feed for several species of mussel feeding sea ducks which have decreased dramatically in numbers. To assess long-tailed ducks exposure to brominated substances, liver tissue from long-tailed ducks wintering in the Baltic Sea and blue mussels were analysed. The result confirms that long-tailed duck are exposed to OH-PBDEs via their diet. However, low concentrations were found in the duck livers, which suggest low retention of these compounds despite daily intake. How the nutritional value of blue mussels as feed for sea ducks are affected by OH-PBDE exposure still needs further studies. Other species of sea ducks foraging on Baltic blue mussels during summer months can also be more exposed due to seasonal variation in primary production.Herring sampled in the Baltic Proper and Bothnian Sea, were found to contain OH-PBDEs and high levels of their methylated counterpart, MeO-PBDEs. As demethylation of MeO-PBDEs is known to occur in fish, MeO-PBDEs may pose as additional source for more toxic OH-PBDEs in herring and their roe.
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| 2. |
- Cantillana, Tatiana, 1969-
(författare)
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Toxicologically important DDT metabolites : Synthesis, enantioselective analysis and kinetics
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- DDT was extensively and globally used as a pesticide in agriculture and for malaria vector control from the 1940’s until the 1970’s. Due to its heavy use, DDT became ubiquitously distributed throughout the environment. DDT and several DDT metabolites are persistent organic pollutants. Two DDT metabolites, 3-MeSO2-DDE and o,p’-DDD have been proved to be tissue specific toxicants in the adrenal cortex. They are bioactivated to reactive intermediates which bind covalently to the adrenal cortex causing cell death. Due to its tissue specific toxicity o,p’-DDD has been used as a chemotherapy drug for adrenal cancer in humans. The efficacy and potency is however low and o,p’-DDD treatment is associated with serious side effects. 3-MeSO2-DDE has been suggested as a potential alternative therapeutic agent. A key aim of this thesis has been to improve the understanding of the kinetics of the two adrenocorticolytic compounds o,p’-DDD, its two enantiomers and 3-MeSO2-DDE. To meet this objective chemical synthesis and enantioselective analysis were required. Furthermore, in vitro toxicity of o,p’-DDD enantiomers and diastereomers were performed. An 11 step synthesis of 3-SH-DDE has been developed to promote both labelled and unlabelled synthesis of 3-alkylsulfonyl-DDE. Toxicokinetic studies showed that 3-MeSO2-DDE and o,p’-DDD were accumulated in tissues and retained in adipose tissue in minipigs. 3-MeSO2-DDE however had a twice as long biological t1/2 and a considerably lower Vd compared to o,p’-DDD. Suckling offspring were more exposed to 3-MeSO2-DDE than their mothers who were given 3-MeSO2-DDE orally. Interindividual differences in enantiomer kinetics in minipigs were observed suggesting polymorphism among the minipigs. Preparative isolation of the o,p’-DDD enantiomers is presented allowing determination of the absolute structures of the o,p’-DDD enantiomers by X-ray. The pure enantiomer of o,p’-DDD showed significant differences in toxicity in human adrenocortical cells.
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| 3. |
- Granelli, Lisa, 1979-
(författare)
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Chemical reactivities as a mirror of environmental transformations - method development and assessment of some selected organohalogens
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The assement of chemical persistence is an important part of legislative protection of the environment and human health. Of the vast number of chemicals on the market today few have been properly assessed. The coordination between testing guidelines from different frameworks is limited and especially the methods for determination of biodegradation show poor reproducibility because of their highly complex nature. In order to circumvent the multifactorial assessment methods that involve the use of e.g. soils and sediments an attempt to create a new approach to chemicals assessment was postulated by Green and Bergman in 2005. This approach puts the focus on testing the chemical reactivity of the compound in environmentally relevant transformation/degradation reactions, i.e. reduction, oxidation, hydrolysis-substitution-elimination (hse), radical reactions, and photolysis. These tests are to be performed in controlled abiotic laboratory experiments ensuring that the results reflect the transformation rate of the intended type of reaction for the investigated substance. To achieve an assessment of the presistence of the compound, the test results are then combined with data on physicochemical properties of the compound and a mathematic matrix describing the reactive power of the different types of reactions in each environmental compartment (air, water, soil, and sediment). Thus far methods for testing of oxidation, photolysis, and hydrolysis-substitution-elimination reactions have been developed. Within this thesis a method for determining reduction was developed and further utilised to determine transformation products from reductive debromination of the three nonabrominated diphenyl ethers. The previously established method for hse was evaluated and further developed in a study of selected chlorobenzenes. Some novel brominated flame retardants were investigated using the previously developed photolysis method, and transformation products and quantum yields were determined. All of the papers presented within this thesis intend to build on the project of a new persistency assessment model. The results presented also contributes important information on the properties and transformation of some common organohalogen pollutants.
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| 4. |
- Löfstrand, Karin, 1980-
(författare)
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Trends and exposure of naturally produced brominated substances in Baltic biota - with focus on OH-PBDEs, MeO-PBDEs and PBDDs
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The semi-enclosed and brackish Baltic Sea has become heavily polluted by nutrients, anthropogenic organic and inorganic chemicals via human activities. Persistent organic pollutants (POPs) have been thoroughly investigated due to their linkage to toxic effects observed in Baltic biota. There has been far less focus on semi-persistent pollutants e.g. naturally produced oraganohalogen compounds (NOCs) and their disturbances in the environment. This thesis is aimed on assessment of levels and trends of naturally produced brominated compounds in Baltic biota; more specifically on hydroxylated polybrominated diphenyl ethers (OH-PBDEs), methoxylated PBDEs (MeO-PBDEs) and polybrominated dibenzo-p-dioxins (PBDDs). These, NOCs, may originate from production in algae and cyanobacteria. OH-PBDEs and MeO-PBDEs may also be formed as metabolites of polybrominated diphenyl ethers (PBDEs), i.e. well-known commercial flame retardants. High levels of OH-PBDEs, MeO-PBDEs and PBDDs are shown within Baltic biota (cyanobacteria, algae, mussels, fish), often in much higher concentrations than PBDEs which are possible anthropogenic precursors of OH- and MeO-PBDEs. The levels of OH-PBDEs, MeO-PBDEs and PBDDs are higher in the Baltic Sea than on the west coast of Sweden. Temporal and seasonal variations show fluctuations in concentrations of OH-PBDEs, MeO-PBDEs and PBDDs, possibly related with macroalgal life-cycles. OH-PBDEs, MeO-PBDEs and PBDDs are present in several filamentous macroalgae species, but considering the levels quantified, the time of peak exposure and the species life-cycle the macroalgae, Pilayella, Ceramium and Cladophora are suggested as major natural producers of OH-PBDEs and PBDDs. The high levels of OH-PBDEs, MeO-PBDEs and PBDDs in the Baltic Sea may affect numerous organisms in the ecosystem. The toxic effects of OH-PBDEs and PBDDs are of particular concern. This thesis stress the importance of assessing and monitoring these substances, since the exposure to OH-PBDEs and PBDDs, during summer, may cause acute effects in Baltic fish and wildlife.
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| 5. |
- Norrgran Engdahl, Jessica, 1979-
(författare)
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Cats as a biomarker for exposure to POPs in home environments : – with focus on brominated chemicals and associations to feline hyperthyroidism
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis, body burden of brominated chemicals such as polybrominated diphenyl ethers (PBDEs) and brominated phenolic substances are explored. The external exposure of cats to these compounds from house dust and their food was also investigated. The analytical methodology used for serum extractions was validated for analysis of OH-PBDEs in cat serum.Cats are highly exposed to dust and thereby also to chemicals accumulated in dust, due to their grooming behavior. This makes pet cats, a suitable biomarker for exposure to chemicals in house dust in home environments. Thereby, cats’ exposure to dust is somewhat similar to toddlers, due their hand-to-mouth behavior. Thus, cats’ internal exposure may be used to access that of toddlers. The PBDE pattern in Swedish pet cats show exposure to Penta-, Octa- and DecaBDE and their profile matches that of dust from their homes, suggesting dust to be an important exposure source. Serum concentrations of BDE-47 in the cats were also shown to correlate with house dust from their living rooms.Feline hyperthyroidism (FH) is a common endocrine disease in elderly cats worldwide, still the actual cause(s) has not been established even though environmental pollutants such as PBDEs have been suggested. Difference in contamination load between cats with normal thyroid status and cats diagnosed with FH was performed and higher serum concentrations for some PBDEs (BDE-99, 153, -183) were found in the hyperthyroid cats.Further, the presence of the longtime discontinued flame retardant, decabromobiphenyl (BB-209) in all sampled cats indicates that it is still being circulated. A significant correlation between serum concentrations of BB-209 and matched cat food samples was found.Very few OH-PBDEs were indeed shown in cat serum and the dominating compound, 6-OH-BDE47, is believed to be of natural origin rather than being a metabolite of BDE-47. A significant correlation between serum concentration of 6-OH-BDE47 and cat food was found.
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| 6. |
- Norström, Karin, 1972-
(författare)
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Bis(4-chlorophenyl) sulfone and PCB methyl sulfone metabolites : Trends and chirality in the Baltic Sea environment
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Baltic Sea was earlier identified as a highly polluted brackish water body and still is. The high concentrations of polychlorinated biphenyls (PCBs), p,p’-DDT and related compounds led to severe effects on several species in the Baltic region. However, the situation has improved significantly since the 1970’s resulting in lower exposures to a range of pollutants and healthier wildlife populations. Independent of this positive trend there are still new chemicals leaking into the Baltic Sea environment. The objective of this thesis is to improve the knowledge of sulfone containing compounds and pollutant metabolites in wildlife, with special interest in bis(4-chlorophenyl) sulfone (BCPS) distribution, temporal trend and exposure levels, and the methylsulfonyl-PCBs (MeSO2-PCBs). The latter are of particular interest for chiral MeSO2-PCBs. BCPS is used for the production of high temperature polymers and was detected as an environmental contaminant ten years ago. PCBs, p,p’-DDT and related compounds are still of scientific interest. BCPS is biomagnified and especially in the bird guillemot which has levels of up to 2000 ng BCPS/g fat compared to the grey seal with concentrations of about 60 ng/g fat. The seal levels are similar to the herring, the prey of the bird and seal, with concentrations of 30 ng BCPS/g fat. The guillemot concentration of BCPS has been similar over the last 30 years with a minimal, but significant, annual decline of 1.6%. The reason for the slow decline is not yet understood. Also MeSO2-PCBs and 3-MeSO2-DDE show a small decrease over time in guillemot egg (3 and 9%, respectively), which is less then for the parent compounds. This shows that the sulfone metabolites are more persistent than their precursors in the guillemot. Furthermore, all these sulfone containing compounds showed a specific retention to liver comparing different tissues in grey seal. The atropisomers of the chiral MeSO2-PCB were analysed in both the guillemot and the grey seal and showed to occur in a skewed relationship. This is particularly pronounced in seals where one atropisomer of each chiral congener is very dominating. The dominating atropisomers have been identified with an absolute R configuration, in both grey seal and guillemot. An enantioselective metabolism was indicated to occur when experimentally tested by CB-132 in rat. This thesis is stressing the high specificity in wildlife for one atropisomer in the pair of chiral PCB methyl sulfones being PCB metabolites, and the high BCPS concentrations in guillemot hatching in the Baltic proper.
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| 7. |
- Strid, Anna, 1978-
(författare)
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Organohalogen contaminants in Greenland shark (Somniosus microcephalus)
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The remote sub-Arctic/Arctic environment has due to human activities become a sink for organohalogen contaminants (OHCs). These OHC include traditional contaminants such as polychlorinated biphenyls (PCBs), DDTs and technical mixtures of polybrominated diphenyl ethers (PBDEs), all included in the Stockholm Convention list of persistent organic pollutants (POPs). Other OHCs, currently under evaluation to be included among the POPs i.e. short chain chlorinated paraffins (SCCPs) and hexabromocyclododecane (HBCDD) are also found in these environments as well as a whole range of other OHCs. The main objective of this thesis is to increase the knowledge about the presence of OHCs in a high trophic Arctic shark species, the Greenland shark (Somniosus microcephalus). The Greenland shark is an opportunistic feeder, occasionally feeding at the top of the Arctic marine food chain. Furthermore may this species have a life span in excess of 100 years and is probably among the oldest of any fish species. These traits make the shark prone to accumulate elevated concentrations of OHCs. This has shown to be true for the Greenland sharks studied and most of the targeted OHCs were determined in the species. The highest concentrations were observed for the DDTs, ranging up to 26 μg/g fat. Other OHCs reported that are of special interest are SCCPs and brominated flame retardants used as replacement products to PBDEs; pentabromoethylbenzene (PBEB) and 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE). Also a range of OHCs whose origin is assumed to be natural, were shown to be present in Greenland sharks. This thesis is stressing the fact that even though the use of certain OHCs has been banned for decades they are still present at high concentrations in the deep waters of the Arctic. Therefore it is of major importance to continue to monitor the fate of traditional and emerging OHCs in the environment, and for this purpose the Greenland shark is an excellent species.
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| 8. |
- Söderström, Maria, 1960-
(författare)
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Local and global contaminants in Swedish waters : studies on PCBs, DDTs, 4,5,6-trichloroguaiacol and their transformation products in fish and sediments
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is focused on studies on the environmental fate and methodological improvements for determination of the global contaminants, PCBs and DDTs, and locally discharged phenolics, e.g. 4,5,6-trichloroguaiacol (4,5,6-TCG), and their transformation products.4,5,6-TCG is released from bleached pulp mills, and was chosen as a model substance, to study its fate and effects in aquatic environments. In a brackish water model ecosystem, 4,5,6-TCG was shown to be transformed via demethylation, dechlorination, and methylation reactions. Marine periphyton exposed to 4,5,6-TCG was shown to form demethylated, brominated and dimeric metabolites. Several of these metabolites were identified and quantified. Also more tightly bound chlorophenolics were recovered from the substrate, after harsh extraction procedures had been applied. Conjugates of chlorophenols in fish bile were determined as useful tracers for monitoring effluents from bleached pulp mills, even in areas far from the discharge point. To facilitate calculations of water concentrations, bile to water bioconcentration factors (bBCF-values) were determined for several phenolics, including also alkali-labile chlorocatechols.PCBs and DDTs, were assessed in Swedish lakes with background exposure of these global contaminants. A methodological study focus on the contamination risks of airborne PCBs, during freeze-drying and storage of dry sediment samples. Eutrophication has been proposed to cause lower levels of pollutants in biota in lakes due to biomass dilution but in this thesis examples of higher levels of PCBs in sediment traps, sediment and in perch, and also in higher fluxes of PCBs to the sediment, were observed. Phytoplankton are supposed to be responsible for most of the transport of the contaminants. The composition of DDTs in soil, sediment traps and in dated sediment cores was studied in some detail. PCBs, DDTs, HCB and HCHs were measured in sediments from 100 reference lakes included in the National Swedish Environmental Program. The lakes have a large variation in lake characteristics, representative for different areas in Sweden. A gradient was observed for sPCB with decreasing levels from the south west towards the north. The results suggests that longrange transport is the dominating mechanism for distribution of the contaminants analysed. In this study the levles of PCBs and DDTs were lower in eutrophic lakes than in oligotrophic lakes, in an area with similar atmospheric exposure.
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| 9. |
- Yin, Ge, 1987-
(författare)
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Organohalogen contaminants in wildlife from the Yangtze River Delta : Development of methods and assessments of legacy and emerging persistent organic pollutants
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 10. |
- Christiansson, Anna, 1977-
(författare)
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Synthesis of highly brominated diphenyl ethers and aspects on photolysis and indoor spreading
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Adding chemicals to materials to decrease flammability can be dated back to as early as 450 BC when the Egyptians used alum to reduce flammability of wood. Almost 2500 years later brominated flame retardants (BFRs) are used to prevent ignition of textiles, electronics and polymers. BFRs in major use today are polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCDD) and tetrabromobisphenol A (TBBPA), including derivatives. There have been three industrial PBDE mixtures produced. Extensive scientific reporting has shown increasing concentrations of PBDEs in wildlife and in humans. This in combination with reports on their physico-chemical characteristics and chemical reactivity have led to that two of the PBDE products have been classified as being persistent, bioaccumulative and toxic, which has led to legislative measures, in e.g. EU, Norway and the USA.The availability of pure reference standards is a prerequisite for much toxicologically related research. Hence the main objective of this thesis was to develop additional methods for synthesis of highly brominated diphenyl ethers. Further, to quantify and identify photolysis products of decabromodiphenyl ether (decaBDE) and to perform a case study regarding PBDE exposure in aircrafts.Synthesis of highly brominated BDE congeners by perbromination of mono- or diaminodiphenyl ethers followed by diazotization of the amino group(s) and introduction of hydrogen(s) in the molecules is a convenient route for synthesis of some octaBDEs and all nonaBDEs. Selective bromination of diaminodiphenyl ether, followed by diazotization of the amino groups and substitution with bromines yielded a hexaBDE or a heptaBDE which were then further brominated to octaBDE congeners.Even though several studies have been performed on photolysis of decaBDE a new study with a more quantitative approach was performed as part of this thesis. Debrominated PBDE products were identified and quantified and a marker PBDE for UV degradation of DecaBDE was identified i.e., 2,2’,3,3’,5,5’,6,6-octabromodiphenyl ether (BDE-202). Polybrominated dibenzofuranes, methoxlated brominated dibenzofuranes, pentabromophenol and hydroxylated bromobenzenes were also detected. The PBDEs accounted for approximately 90% of the total amount of substances in each sample and the PBDFs for about 10%. Also, a case study on potential exposure to PBDEs in humans travelling long distances by aircraft was done. It was shown that PBDE concentrations in dust onboard aircrafts may be high and increased PBDE serum levels were indicated in a majority of the travellers.The present thesis has contributed to make higher brominated diphenyl ethers available as reference standards, allowing better quantitative assessments possible regarding both abiotic studies and exposure assessments. New toxicological testing can also be pursued.
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| 11. |
- Fång, Johan, 1981-
(författare)
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Persistent halogenated pollutants in mothers´ milk
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Persistent organic pollutants (POPs) are substances that degrade slowly, are distributed wotldwide, bioaccumulate and are harmful to both animals and humans. The release of POPs to the environment was the preamble to human background contamination. In the mid-20th century it became clear to scientists and policy makers that even the mothers´ milk was contaminated by POPs. This led to national and global monitoring programs to assess the extent of contamination and subsequently to ban several POPs via the Stockholm Convention.The concentrations of dioxin, polychlorinated dibenzodioxins (PCDD), -furans (PCDF) and dioxin like polychlorinated biphenyls (DL-PCB) is analysed in a retrospektive time trend study. The findings show a faster decrease of dioxin concentrations 2002-2011, compared to the whole series, 1972-2011. The transfer of polybrominated diphenyl ethers from mother to child via the milk is investigated and a relationship between both the PBDE molecule’s size and time post partum of the sampling and the ability to transfer to the milk is found. A literature review concerning the POPs in human milk finds, in addition to accounting for POP concentrations; that some substances are investigated more thoroughly than others; DDT and PCB compared to Aldrine and Toxaphene and that certain geographical areas are more well-studied than others, e.g. Europe compared to Africa. The study also shows a strong over all need for better reporting protocols. To understand the current and emerging POPs present in mothers´ milk screening of a larger than normal sample of mothers´ milk can give new insights. The development of a method designed to tackle the problems of large fat rich sample and still to be as benign as possible to the analytes was undertaken. The method is subsequently applied to a both Swedish and Chinese pooled sample to show the differences in POP exposure between countries.
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| 12. |
- Hofvander, Lotta, 1965-
(författare)
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Polychlorinated biphenyls and their metabolites in human blood : Method development, identification and quantification
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- PCBs are well known environmental pollutants. They are also precursors to metabolites, as the hydroxy-PCBs and the methylsulfonyl-PCBs. This thesis presents a validated methodology for analysis of PCB metabolites and a structural identification of 38 hydroxy-PCBs in human blood. Further methodological development resulted in an identification of a similar number of methylsulfonyl-PCBs.The analytical method has been applied in two extensive studies of humans, consisting of maternal and cord blood from Dutch women and of blood from humans living in Slovakia. The Dutch shows that the relative transfer of hydroxy-PCBs from the mother to the foetus is higher compared to the PCBs. Even though the chemical plant in Michalovce in Slovakia had been shut down for over 20 years, the concentrations of PCB and its metabolites were among the highest detected in European human blood.
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| 13. |
- Licea Pérez, Hermes, 1969-
(författare)
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In vivo dosimetry of some important industrial chemicals by measurement of their reaction products with hemoglobin
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hemoglobin adduct measurements provide a useful tool for the development of models for risk assessment of chemicals. The measurements can be used to identify reactive metabolites and to determine the in vivo doses of these metabolites. Thus, the need to use default assumptions with regard to animal metabolism and dose-response relationships can be reduced. The research presented here involved the study of a number of important industrial chemicals, primarily 1,3-butadiene, glycidyl ethers, acrylonitrile and acrylamide. Many of these chemicals were shown to be mutagenic in several tests (in vivo/in vitro) and are carcinogenic in experimental animals. The compounds or their metabolites have the ability to react with DNA to form adducts. Formation of such adducts is believed to be responsible for the development of mutation and cancer. The main aim has been to study relationships between exposure and in vivo dose. In some cases analytical methods to measure hemoglobin adducts were already available (for acrylonitrile and acrylamide) or were relatively straightforward (for some glycidyl ethers). In other cases considerable method development was required (for reactive metabolites of 1,3-butadiene, allyl glycidyl ether and acrylamide). The hemoglobin adducts analyzed in the present study are formed from the electrophilic moiety of the compound of interest with N-terminal valine in hemoglobin. The analysis and quantification of these adducts was achieved by derivatization with pentafluorophenyl isothiocyanate, in some cases followed by acetylation, and analysis of the corresponding pentafluorophenylthiohydantoin derivatives by GC/MS or GC/MS-MS. The methods have been applied for dosimetry in experimental animals as well as for biomonitoring exposure in human populations. Discussions in the literature on the carcinogenicity of 1,3-butadiene have been focused on its metabolites diepoxybutane and 1,2-epoxy-3-butene. Our results show that 3,4-epoxy-1,2-butanediol is an important metabolite of 1,3-butadiene. Another important outcome of the studies was that the double bond of allyl glycidyl ether is metabolized to a reactive epoxide in mice. This means that a bifunctional alkylating agent, diglycidyl ether, could possibly be formed. Bifunctional alkylating agents are usually more biologically effective than monofunctional compounds. Data obtained from this research will help to better understand the mechanism of toxicity of the chemicals under study and to provide an improved basis for risk estimation.
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| 14. |
- Linderholm, Linda, 1978-
(författare)
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Assessment of Environmental Pollutants in Humans from Four Continents : Exposure levels in Slovakia, Guinea-Bissau, Nicaragua and Bangladesh
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Humans are continuously exposed to complex mixtures of anthropogenic chemicals. This thesis focus on human exposure to persistent organic pollutants (POPs). POPs ability to bioaccumulate and biomagnify together with the extensive historical use of POPs in e.g. agriculture and industry have resulted in detection of these compounds in humans and animals from all over the world. Adverse health effects caused by POPs are of particular concern for newborns and young individuals. The objective of this thesis is to assess human exposure to a selected set of POPs and their metabolites. More specifically, one aim of my thesis is to determine the exposure to polychlorinated biphenyls (PCBs) and in particular their methylsulfonyl and hydroxylated metabolites in humans from a “hot-spot” area of PCB contamination in eastern Slovakia. The maternal transfer of these chemicals is studied. Further, another specific aim is to determine occurrence, levels and, when possible, temporal trends of POPs in children and adults from three developing countries, Nicaragua, Guinea-Bissau and Bangladesh. High concentrations of PCBs and their metabolites are shown in men and women from Michalovce in eastern Slovakia. Placental transfer of methylsulfonyl-metabolites of PCBs and 4,4’-DDE was observed for the first time. Decreasing temporal trends of the majority of POPs are shown in serum from a cohort of policemen from Guinea-Bissau. In contrast, the levels of polybrominated diphenyl ethers (PBDEs) show an increasing time trend. Within five years, decreasing levels of POPs were also shown in children working and living at a waste disposal site in Nicaragua. Children working and living at waste disposal sites in Bangladesh have considerably lower levels of POPs compared to the children from Nicaragua except for 4,4’-DDT and 4,4’-DDE that are present at very high concentrations, indicating ongoing use of technical DDT. There are many studies on levels and trends of environmental pollutants from the developed industrial countries in the world, whereas data from developing countries is still scarce. This thesis contributes to partly fill this data gap since it includes assessments of POPs in children and adults from four countries on four continents.
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| 15. |
- Malmberg, Tina, 1964-
(författare)
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Identification and Characterisation of Hydroxylated PCB and PBDE Metabolites in Blood : Congener specific synthesis and analysis
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hydroxylated polychlorinated biphenyls (OH-PCBs) are known metabolites of polychlorinated biphenyls (PCBs) in many mammalian, bird and fish species. Among those, certain OH-PCB congeners are strongly localised in the blood compartment of humans and wild animals. This retention is believed to mainly be a consequence of their high affinity to transthyretin (TTR), a thyroid hormone transport protein, as shown by in vitro binding studies. Polybrominated diphenyls ethers (PBDEs), used as flame retardants, are another group of compounds that forms hydroxylated metabolites (OH-PBDEs), which have been shown in rodents and fish. OH-PBDEs, in difference with OH-PCBs, also exist as natural products, produced by e.g. marine sponges. Several OH-PBDE congeners that have been identified in marine environmental samples seem to originate, to major part, from the natural production of these compounds.An aim of this work was to develop methods and prepare individual OH-PCB congeners for making them available as analytical standards for qualitative identification of OH-PCBs in human blood. Also the issue of OH-PBDE retention in blood after PBDE exposure was addressed in an experimental study. Further, the aim was to characterise selected, individual OH-PCBs and OH-PBDEs by measuring their dissociation constants, octanol water partitioning and affinity for TTR. A study on the kinetics of two environmental abundant OH-PCBs, 4-OH-CB107 and 4-OH-CB187 was performed in the rat.About 50 OH-PCB congeners, analysed as their corresponding methyl derivatives, were detected in a pooled blood sample from Swedish males. Thirty-eight OH-PCBs were structurally identified by comparison with 60 authentic individual MeO-PCB standards. Twenty of the MeO-PCB standards were prepared for the identification work. A method has been developed for preparation of a critical intermediate for synthesis of meta-OH substituted OH-PCBs. The calculated plasma half-lives of 4-OH-CB107 and 4-OH-CB187 in rat were shown to be 3.8 days and 15 days, respectively. Dissociation constants for selected OH-PCBs and OH-PBDEs were determined in a methanol/water mixture and psKa values ranged from 5.1 to 7.3, with lower psKa values for the OH-PCBs than the OH-PBDEs. All tested compounds in the TTR in vitro assay showed higher affinity towards TTR than the natural ligand, thyroxine, except for 4-OH-CB199 and 6-OH-BDE47. Sixteen OH-PBDE and two diOH-PBDE metabolites were detected in the plasma of rats after exposure of seven PBDE congeners which of four OH-tetraBDEs were structurally identified. The OH-PBDE metabolites were entirely dominated by meta- and para-substitution of the hydroxy group. The results indicate that OH-PBDE congeners have the ability to be retained in rat blood.
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| 16. |
- Rahm, Sara, 1972-
(författare)
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Hydrolysis and photolysis of brominated flame retardants and some traditional persistent organic pollutants : Reactivity as a tool in fate assessement of chemicals
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- An organic compound that remains in the environment for a long time is regarded as a persistent organic pollutant (POP). Still, persistency is not a well defined property with a firm definition. Instead it is a conceptual property of chemicals for which DDT and PCB are typical representatives. No organic chemicals in the environment are inert and are thus subjected to chemical transformation reactions in air, water, soil sediments and in biota. Environmental pollutants are distributed in the environment based on their physicochemical properties and their reactivity. While the former properties have been thoroughly studied and used in modelling of the fate of chemicals in the environment, the latter property – reactivity – has been investigated poorly. The far-reaching objective with the present thesis is to introduce the reactivity of chemicals into the concept of persistency. More specifically the aim is to develop methodologies for defining chemical reactivity by determination of disappearance reaction constants for hydrolysis and photolysis of actual or potential environmental contaminants. Other transformation reactions in the environment such as oxidations reductions and radical reactions are not included at this stage. In this thesis, hydrolysis include both substitution and elimination reactions. The developmental work is performed largely by comparing the reactivity of brominated flame retardants but also include several traditional contaminants for comparative reasons. A new method for determination of the rate of hydrolysis of chemicals is developed using methoxide in methanol and DMF, which is done by using hexachlorobenzene (HCB) as the test chemical. The method is applied to several other chemicals, particularly polybrominated diphenyl ethers (PBDEs) but also traditional POPs. Chemicals such as DDT,TBBPA 2,3-dibromopropyl ether react very fast and the perbrominated diphenyl ether (BDE-209) is shown to undergo nucleophilic aromatic substitution faster than HCB. Compounds that can undergo elimination are rapidly degraded while the rates of substitution reactions of aromatic chemicals depend on the degree of halogenation. A new method is used for studying photolytic reactions based on irradiation of UV light at environmentally relevant wavelengths and with the study compounds dissolved in methanol/water (4:1). Disappearance constants and quantum yields are determined for several traditional and potential environmental contaminants. Halogenated phenols are rapidly transformed under these conditions. Polybrominated aromatics are indicated to react faster than the corresponding chlorinated compounds. The two methods for studying reactivity of chemicals have the potential of being useful to predict the persistency of chemicals in the environment. Such predictions must however also include the compound’s susceptibility to oxidation, reduction and radical reactions in all major environmental compartments and knowledge of their physicochemical characteristics.
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| 17. |
- Sundström, Maria, 1980-
(författare)
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Radiosynthesis of Perfluoroalkyl Substances : Chemical analysis, uptake, distribution, and partitioning studies
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Perfluoroalkyl substances (PFASs) are widely utilized manmade chemicals. Their properties have made them highly appreciated in a variety of industrial and consumer product applications, including fire-fighting foams, hydraulic fluids, as well as in cookware and food contact papers.However, some of the PFASs are highly persistent in the environment and their toxicological profiles are of concern. Voluntary and regulatory efforts have been taken to reduce the environmental levels of PFASs. These actions have resulted in a reduction of PFASs in human milk from Stockholm as presented in this thesis.The radiosyntheses of 35S-PFOS, 35S-PFBS, and 14C-PFOA presented herein were applied for distribution studies in mice but also for solubility and adhesion experiments of common laboratory solvents and buffers. The radiosynthesis employed reactive Grignard reagents, perfluoroalkyliodides, and 35S-sulfur dioxide or 14C-carbon dioxide. The distribution studies were performed with 35S-PFOS on both pregnant mice and their offspring as well as on male mice. The mice were subjected to whole-body autoradiography and the tissues were analyzed by liquid scintillation counting. Liver and lungs were the target organs for 35S-PFOS in the dams. The fetuses and pups had remarkable high levels of 35S-PFOS in their lungs as well as in the brain. The male mice were given a high dose and a more environmental relevant dose of 35S-PFOS. PFOS was transferred from the blood to the tissues as the dose increased.In another study the distribution pattern of the shorter homologue PFBS was compared to PFOS. 35S-PFBS was utilized and demonstrated a 5-40 fold lower tissue levels in comparison to PFOS.The pharmacokinetic parameters determined for PFHxS in mice, rats, and monkeys will provide valuable insight in establishing a proper risk assessment for this compound. The study confirms the common species differences in serum elimination half-life that are associated with PFASs.
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| 18. |
- Waldebäck, Monica, 1941-
(författare)
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Pressurized Fluid Extraction : A Sustainable Technique with Added Values
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The challenge for the future was defined by the Brundtland Commission (1987) and by the Rio Declaration (1992), in which the fundamental principles for achieving a sustainable development were provided. Sustainable chemistry can be defined as the contribution of chemistry to the implementation of the Rio Declaration. This thesis shows how Pressurized Fluid Extraction (PFE) can be utilized in chemical analysis, and how this correlates to Green Chemistry.The reliability and efficiency of the PFE technique was investigated for a variety of analytes and matrices. Applications discussed include: the extraction of the antioxidant Irganox 1076 from linear low density polyethylene, mobile forms of phosphorus in lake sediment, chlorinated paraffins from source-separated household waste, general analytical method for pesticide residues in rape seed, total lipid content in cod muscle, and squalene in olive biomass. Improved or comparable extraction yields were achieved with reduced time and solvent consumption. The decrease in use of organic solvents was 50-90%, resulting in minimal volatile organic compounds emissions and less health-work problem. Due to higher extraction temperatures and more efficient extractions, the selection of solvent is not as important as at lower temperatures, which makes it possible to choose less costly, more environmentally and health beneficial solvents. In general, extraction times are reduced to minutes compared to several hours. As a result of the very short extraction times, the amount of co-extracted material is relatively low, resulting in fewer clean-up step and much shorter analysis time. Selective extractions could be obtained by varying the solvent or solvent mixture and/or using adsorbents.In this thesis, the PFE technique was compared to the twelve principles of Green Chemistry, and it was shown that it follows several of the principles, thus giving a major contribution to sustainable chemistry.
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