| 61. |
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| 62. |
- Cantillana, T., 1969-, et al.
(författare)
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Synthesis of 2-(4-chlorophenyl)-2-(4-chloro-3-thiophenol)-1,1-dichloroethene (3-SH-DDE) via Newman-Kwart rearrangement - A precursor for synthesis of radiolabeled and unlabeled alkylsulfonyl-DDEs
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- For the first time, a pathway for synthesis of 2-(4-chlorophenyl)-2-(4-chloro-3-thiophenol)-1,1-dichloroethene (3-SH-DDE), is presented. The compound is of particular interest as a precursor for synthesis of alkylsulfonyl-DDE containing different alkyl groups to discover structural activity relationships, and to promote synthesis of radiolabeled methylsulfonyl-DDE. 2-Chloro-5-methylphenol was first methylated and further oxidized to the corresponding benzoic acid. The acid was reduced to the corresponding aldehyde (4-chloro-3-methoxy benzaldehyde) via 4-chloro-3-methoxy-benzene methanol. A lead/aluminium bimetal system was used to carry out the reductive addition of tetrachloromethane to 4-chloro-3-methoxy benzaldehyde to obtain 2,2,2-trichloro-1-(4-chloro-3-methoxyphenyl)ethanol, the desired starting material to synthesize the DDT-analogue (2-(4-chlorophenyl)-2-(4-chloro-3-methoxy-phenyl)-1,1,1-trichloroethane). Elimination of hydrochloric acid and removal of the methyl group led to the 3-OH-DDE. The Newman-Kwart rearrangement was applied to convert 3-OH-DDE to 3-SH-DDE via the dimethylcarbamothioate derivative. 3-SH-DDE is then used as a precursor for the radiolabel synthesis. The overall yield to acquire 3-SH-DDE after 11 steps was 3%. The step with the lowest yield was the DDT-analog synthesis with a yield of 30%. All other step had a yield of >50%. 3-SH-DDE was methylated with 14C-labeled iodomethane and oxidized by hydrogen peroxide to obtain 3-[14C]MeSO2-DDE in an overall yield of 30%.
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| 63. |
- Cantillana, T., 1969-, et al.
(författare)
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Toxicokinetics of the CYP11B1-activated adrenal toxicant 3-MeSO2-DDE in mother and offspring following oral administration to lactating minipigs
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- 3-Methylsulfonyl-4,4’-DDE (3-MeSO2-DDE) is a persistent and bioaccumulative metabolite of 4,4’-DDT, formed through biotransformation of 4,4’-DDE and characterized by a high and tissue-specific toxicity in the adrenal cortex in mouse fetuses, suckling pups and adult mice. 3-MeSO2-DDE also targets the human adrenal cortex kept in tissue-culture ex-vivo and human adrenocortical H295R cells in vitro. The present study was designed to examine the excretion of 3-MeSO2-DDE in milk and the maternal and neonatal toxicokinetics following a single oral dose to lactating minipigs. Milk, maternal fat, and plasma from five pigs and their suckling offspring were collected at regular intervals during four weeks. At autopsy on day 30 post partum, adrenals, liver and body fat were sampled from mothers and piglets. The levels of 3-MeSO2-DDE were measured by gas chromatography and the toxicokinetics in mothers and offspring were computed. The levels of 3-MeSO2-DDE in milk were considerably higher than in maternal and offspring plasma throughout the investigation. Based on both fresh weight and fat contents, the 3-MeSO2-DDE plasma levels in the piglets were about five times higher than in the mothers. A strong accumulation of 3-MeSO2-DDE was observed in fat tissue and a moderate accumulation in adrenals and liver of mothers and offspring. The retained tissue levels in the piglets were consistently higher than in the mothers. It is concluded that suckling offspring were more exposed than their mothers, which were given 3-MeSO2-DDE orally. The results suggest that human risk assessment of the adrenocorticolytic environmental pollutant 3-MeSO2-DDE should be focussed on breast-fed infants. Also in highly 4,4’-DDE- and 3-MeSO2-DDE-exposed marine mammals, the risks posed by 3-MeSO2-DDE are likely most pronounced during the postnatal period
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| 64. |
- 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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| 65. |
- 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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| 66. |
- Clancy, Gunilla, 1968, et al.
(författare)
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Assessing sustainability already in product development
- 2011
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Ingår i: Poster presentation at The Adlerbert Research Foundation Jubilee Conference, 22 November 2011, Göteborg, Sweden. ; , s. 1-
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Since companies need to develop more sustainable products to stay in business in the long term, there is a demand for ways to assess and compare product sustainability already in product development. This is studied through action research performed within the “wood based diaper” material development project (WooDi) aiming to develop a wood based material to replace a petroleum based while ensuring a more sustainable product. Approaches for environmental improvement in product development focus primarily on optimisation of the existing product system, e.g. on replacing parts or processes representing large environmental impacts. In some cases, broader system effects and effects of a changing surrounding system is taken into account e.g. by consequential LCA studies. Such approaches will result in marginal improvements compared to the present situation, and cannot fully take advantage of truly innovative ideas that are based on completely different solutions or the fact that a more sustainable future society might put very different demands on products compared to the strictest environmental requirements of today. Based on what was found in relevant literature, most often lists of predetermined parameters are being used without critical reflection on their importance in light of the specific situation. There is a specific lack of parameters describing the sustainability impacts of a shift from fossil to biomass resources in a life cycle perspective, e.g. related to competition for resources. As a result, an approach for establishing relevant product sustainability parameters is presented, emphasising the need to bringing in the diverse knowledge and experiences of the product development team members as vital for a successful result. The parameters are intended to guide product development as well as to be a base for a sustainability comparison of a new product with a current product.
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| 67. |
- Clancy, Gunilla, 1968, et al.
(författare)
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Consequences for wood resource use for incontinence diapers in Europe 2010 to 2050
- 2011
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Ingår i: Annual Poster Exhibition at the Department of Chemical and Biological Engineering, Chalmers University of Technology, April 12th 2011, Göteborg, Sweden, A7.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Increasing life expectancy results in an ageing society in parts of the world. The old of tomorrow are also expected to have higher comfort demands. One likely consequence is an increase in the need of such products as disposable incontinence diapers, which are today partly based on cellulose from forestry. A calculation of the potential increase for heavy incontinence care (assuming the use of disposable incontinence diapers) was made based on the demographic trends for Europe and on the yield from forestry performed under Nordic conditions. The calculation is using a parameterisation known from literature: I = i * m * u * P. It expresses the impact (I, in our case, forest area in ha) as a product of four factors that humans have the ability to change, in our case, i = ha Nordic forest area / kg material, m = kg material / service, u = service / population in Europe, and P = population in Europe. The 'service' is to keep a customer with heavy incontinence dry for a year, assuming that the same fraction of the population above 50 years as today will need heavy incontinence protection. Under these assumptions, the forest area needed for heavy incontinence care in Europe will increase with about 75% until 2050. According to the current work in the WooDi research project, aiming at producing a wood-based diaper, if the petroleum-based material in the absorbent core in the diapers were to be replaced by wood-based, this would increase the needed forest area to about 136%, assuming a 1:1 replacement ratio by weight which seems to be a low estimate. This is still a small share of the total European forest area (0.2%). However, such an increase in wood demand for only one product is not without problems, since forests to a large extent are already utilised, e.g. for timber and pulp and paper production, and since there is an expected increase in demand for bio-based fuels and materials for replacement of fossil-based products, thus competing for either the yield from the forests or for the land area. At the same time, there are rising concerns regarding biodiversity and other ecosystem services in connection to forestry.
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| 68. |
- Clancy, Gunilla, 1968, et al.
(författare)
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To develop material for more sustainable products: Learning for action
- 2012
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Ingår i: Science and Technology Day 2012, Poster Exhibition at the Department of Chemical and Biological Engineering, Chalmers University of Technology and the Department of Chemistry and Molecular Biology, University of Gothenburg, Göteborg, Sweden, March 27th 2012.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Since companies have to develop more sustainable products to continue operation in the long term, there is a demand for ways to guide and compare the sustainability already in material or product development. This has been studied through action research in a material development project that aims to develop wood-based materials to replace petroleum-based materials while ensuring a more sustainable product. More sustainable future societies might put very different demands on products compared to the strictest requirements of today. To develop more sustainable products therefore requires future oriented assessment parameters already in early stages of material or product development - where choices determining many of the sustainability burdens of a product are made. Furthermore, the whole life cycle of products needs to be envisaged in order for sustainability to be defined. There is thus, for example, little point in talking about 'sustainable materials' since the sustainability of their use may be strongly affected by the rest of the life cycle, after material manufacturing, thus, the materials need to be seen in a context. A description of important sustainability considerations must be made in relation to the challenges that become visible when looking at a whole product system and in relation to its surrounding world which to complicate this further, are also changing over time, and therefore an appropriate time perspective must be applied. Relevant product sustainability aspects and parameters must be identified and described. Approaches for handling this complex situation has not been found in literature and therefore a team learning approach that deal with these issues has been developed. The proposed approach is aimed for material or product development. It has a specific focus on facilitating innovation towards more sustainable products by translating and integrating significant product sustainability characteristics into each team member’s specific area of expertise and everyday work. The material and product development team members are largely affecting the sustainability performance of the finished product. The approach is an iterative process which should continue until the material or product is available for sale and thus the product sustainability parameters will be modified during the process to include new knowledge. Hence, the assessments will be more exact with time.
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| 69. |
- Davies, Ronnie, 1966-
(författare)
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New approaches for synthesis and analysis of adducts to N-terminal valine in hemoglobin from isocyanates, aldehydes, methyl vinyl ketone and diepoxybutane
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Human exposure to harmful compounds in the environment, from intake via food, occupational exposures or other sources, could have health implications. Exposure to reactive compounds/metabolites can be identified and quantified as hemoglobin (Hb) adducts by mass spectrometry. This thesis aimed at improved synthetic pathways for reference standards, and improved analytical methods for adducts to N-terminal valine in Hb from a range of reactive compounds; isocyanates, aldehydes, methyl vinyl ketone (MVK), and diepoxybutane (DEB).Isocyanates form urea adducts with N-terminal valine by carbamoylation, which are detachable as hydantoins by hydrolysis. A new synthetic pathway for reference standards of adducts from isocyanates and a method for their analysis by liquid chromatography/mass spectrometry (LC/MS) were developed.Aldehydes form reversible imines (Schiff bases) with N-termini in Hb. After stabilisation by reduction and detachment by isothiocyanates using modified Edman methods, these adducts could be analysed by gas chromatography/mass spectrometry (GC/MS) or LC/MS. 5-Hydroxymethylfurfural, its metabolites, and other aldehydes related to exposure via food, were studied with regard to analysis by these methods with synthesised standard references. A considerably improved analytical method for imines was developed. Many of the studied adducts are too short-lived in vivo or in vitro to be used for long-term biomonitoring. However, different approaches for the analysis were evaluated.Through synthesised reference standards, an observed unknown adduct in blood was verified as the adduct from MVK. There exist both natural and anthropogenic sources for MVK.DEB, metabolite of butadiene, forms a cyclic adduct to valine-N. A new approach using hydrazinolysis of protein and enrichment by molecularly imprinted solid-phase extraction was tested on synthesised reference DEB-adduct and gave promising results.Synthesised standards were characterized by NMR, LC/MS and GC/MS.
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| 70. |
- de Reijer, Guido J.L. 1997
(författare)
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Catalyst Design for the Valorisation of Biomass-derived Furans into Aromatics
- 2023
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Anno 2023, mankind must strive towards a more sustainable chemical industry; one that does not solely rely on fossil fuels but also utilises renewable feedstocks such as biomass. Biomass can be catalytically converted into commodity chemicals such as aromatics, through intermediates like furans. Aromatics serve as building blocks for everyday materials. In this work, the conversion of one type of furans, 2,5-dimethylfuran, was studied at elevated temperatures in a flow reactor by using a selection of microporous, acidic catalysts. The effluent gas stream was analysed with Fourier-transform infrared spectroscopy and mass spectrometry. Zeolitic catalysts with the MFI-framework were synthesised bottom-up through hydrothermal synthesis, with aluminium or gallium substituted in their framework. Structural analysis was performed comprising X-ray fluorescence, X-ray diffraction, physisorption, thermogravimetric analysis, scanning electron microscopy, and acidity analysis by NH3-TPD. Both aluminium and gallium-substituted zeolites were active for converting 2,5-dimethylfuran into aromatics, of which Ga-MFI displayed superior benzene production and catalyst lifetime. Catalyst deactivation was caused by the loss of strong and extra-framework acid sites due to the coking. After deactivation towards aromatics, the intermediate products formed on weak acid sites such as 2,4-dimethylfuran, were detected as the main products. It was found that an increase in gallium content increases catalytic activity until a limit of Si/Ga=13 was reached, at which the synthesis of the catalyst also yielded an inactive, amorphous phase. Increasing the crystallisation duration enabled approaching this limit and forming phase-pure MFI zeolite with a Si/Ga ratio of Si/Ga=17. Mesopores were introduced to the catalyst to improve the mass transfer of reactants and products. Even though the total production of aromatics and the catalyst lifetime remained unchanged, its number of acid sites was halved implying that each acid site was able to produce twice as many aromatics.
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