| 1. |
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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. |
- 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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| 4. |
- 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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| 5. |
- Eriksson, Johan, 1956-
(författare)
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Polybrominated diphenyl ethers and Tetrabromobisphenol A : Chemical synthesis, X-ray crystallography and Photochemical degradation
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the 1960s’ several manmade chemicals were detected in the environment, far from their sources. The most well known, and most likely those with the largest impact on the society, were DDT and its related compounds, and PCBs. These anthropogenic compounds were characterised as persistent organic pollutants (POPs). Following these POPs, several other chemicals have found their way to the environment. Over the last two decades, brominated flame retardants (BFRs) have become a matter of concern. Among all BFRs being commercially produced, tetrabromobisphenol A (TBBPA) and polybrominated diphenyl ethers (PBDEs) are the ones with the largest annual production. TBBPA is a very well defined compound while PBDEs consist of a large number of isomers and homologues (congeners). TBBPA does not seem to accumulate in biota as the PBDEs do, but is still of concern since it is found in e.g. sediments. The PBDEs can reach accumulation levels up in the ppm range. Still there is a lack of basic data for both TBBPA and PBDEs. Hence the present thesis is aimed to fill some of the data gaps by pursuing work on 1) photochemical degradation of TBBPA, some related compounds, and PBDEs; 2) synthesis of PBDE congeners and of TBBPA degradation products and 3) structural identifications of a selected set of BFRs by X-ray crystallography.An apparatus was designed for carrying out photochemical degradation test of chemicals in general but in particular for BFRs. Quantum yield, rate of degradation and to some extent, identification of degradation products were performed on TBBPA, the corresponding chlorinated compound and a number of TBBPA degradation products and on 15 single PBDE congeners. In order to make this work possible all three nonaBDE isomers were synthesised via a reductive pathway applying sodium borohydride as a reducing agent. The three nona-BDEs were all characterised by X-ray crystallography. The results of the photochemical degradation of TBBPA in water show a rapidly degradable compound also at pH’s that are environmentally relevant. Hence it is likely that TBBPA is not transported long distances, when exposed to sunlight, without undergoing photochemical degradation. It is notable that the TBBPA is degraded through cleavage between the two phenol rings. When the method was applied to study quantum yields and rate constants for the reaction of PBDE congeners it is evident that the decabromodiphenyl ether (BDE-209) is rapidly transformed. The reaction rate differ drastically from PBDEs with four or five bromine substituents that have very long half-lives when subjected to UV-light under the same conditions as for BDE-209. Lower brominated diphenyl ethers and polybrominated dibenzofurans were identified as PBDE degradation products. The synthesis of PBDEs and of TBBPA degradation products expanded the study as did the X-ray structure identifications.
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| 6. |
- 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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| 7. |
- Fängström, Britta, 1969-
(författare)
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Human exposure to organohalogen compounds in the Faroe Islands
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Faroe Islands in the North Atlantic are part of the sub-Arctic region, a remote region far from industrial activity. In spite of this remoteness, the Islands are not a sanctuary: exposures and effects of environmental pollutants mar its natural beauty and wildlife. In the Arctic regions, fish, sea mammals and seabirds have shown to contain elevated levels of the classical persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs), as well as more recent POPs such as the polybrominated diphenyl ethers (PBDEs). Human populations living in the Arctic regions are usually highly dependent on seafood and seabirds as food sources, and diet becomes their major source of exposures to POPs. As reported in the 1980’s, residents of the Faroe Islands were shown to have high concentrations of organohalogen substances (OHS) in their breast milk. Long-finned pilot whales (Globicephala melas) blubber and meat have been shown to be a major source of OHS exposure for some of the Faroe Islanders.The main objective of this thesis is to investigate the sources and concentrations of some POPs and their metabolites for the Faroese population. First, human milk and serum from pregnant women (mothers) and children were analyzed for PBDEs, PCBs, and polychlorinated biphenylols (OH-PCB), the major PCB metabolites. Second, POPs were measured in seabirds, i.e. PCBs in fulmars (Fulmarus glacialis) and guillemots (Uria algae), and PBDEs in fulmars to search for other potential sources of POPs exposure.The results reinforce previous findings that part of the Faroe Island population is highly exposed to OHS. Median concentrations (430 ng/g lipid weight (l.w.) of CB-153) in maternal serum (1994-95) are among the highest in the world. Serum concentrations of CB-153 in children (age 7, samples collected in the early 2000’s) were approximately 90% of those in the mothers, sampled 1994-95. Similarly high CB-153 concentrations (380 ng/g l.w.) were measured in samples of mother’s milk, collected in 1999. The OH-PCB concentrations were also high in segments of the population, with 2.9 ng/g fresh weight as the sum of five OH-PCBs. Except for 4-OH-CB107, concentrations of OH-PCBs were generally lower in children than in mothers.The ΣPBDE median concentrations in maternal serum and human milk (1999) are at the higher end of those reported in Europe, with levels of 9.5 and 8.2 ng/g l.w. respectively. ΣPBDE levels increase in human milk samples collected at three different time points (1987-1999), mainly due to increasing BDE-153 concentrations. The range of serum ΣPBDE concentrations in mothers and children are similar, although the congener patterns show differences. BDE-47 is the dominant congener in maternal serum, while BDE-153 is the major congener in children. The differences seen in PBDE congener patterns may arise differences in dates of sampling (7 years) for the two populations, maternal serum sampled in 1994-95 and children serum sampled in 2000-01, rather than from differences in uptake/metabolism or in contemporary exposures.PCB concentrations in fulmars and pilot whales show similar ranges. In contrast, PBDE concentrations are 100 times higher in pilot whales than in fulmars. Consequently, Faroese may be especially exposed to PCBs via consumption of fulmars and fulmar eggs, while the exposure to PBDEs is less pronounced.Results from this thesis highlight the pronounced exposures to PCBs, OH-PCBs, and PBDEs among residents of the Faroe Islands, a remote region in the Northern Atlantic far away from industrial and urban sources of pollution.
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| 8. |
- 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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| 9. |
- 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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| 10. |
- Jörundsdóttir, Hrönn, 1978-
(författare)
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Temporal and spatial trends of organohalogens in guillemot (Uria aalge) from North Western Europe
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Arctic and sub-Arctic region of the North Atlantic is a remote area, also in relations to environmental contaminants, such as POPs, BFRs and last but not least, PFCs. Both the BFRs and PFCs are considered emerging pollutants of significant environmental concern.The main objective of this thesis is to increase the knowledge and understanding of organohalogen compound distribution in the Nordic environment, their occurrence in biota and change over time. The temporal change of environmental contaminants in the Baltic Sea was monitored over the years 1971 to 2001, with emphasis on BCPS. Further, the pollution profile of the Nordic region was investigated by using common guillemot eggs. Further, to investigate a single remote site, Iceland, in more depth, eggs from seven marine bird species were collected and analysed. Both the organohalogen compounds mentioned above and their metabolites were investigated. The study focused also on an inter-species difference in the bird’s capability of metabolising xenobiotics.All environmental pollutants investigated in the Baltic Sea show decreasing levels over the time period investigated. BCPS showed a remarkably small change over time compared to other compounds. These results reinforce the previous findings, indicating the North Atlantic as remote where the concentrations of the organohalogens are lower compared to Europe in general. There are some exceptions however; the concentration of HCB is ubiquitously distributed across the study area. Further, the spatial trends of the PFCs are complicated and differ within the PFC group. When comparing bird species from Iceland, the concentration of organohalogens mainly depends on trophic level, while migration seems to contribute to a lesser extent. There are some similarities in the metabolism between the bird species investigated. However, the guillemot seems to distinguish itself from other marine birds, with a different composition of metabolites, indicating a different metabolic capacity.In conclusion, even human populations living in remote areas need to minimise the release of pollutants to the environment. Long term, well organised, and extensive governmental monitoring programs are highly recommended to follow the quality the environment and to detect any immediate and/or new threats of chemical pollutants.
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