Biomarkers of internal exposure/dose : Methods to quantify adducts to protein and DNA by LC/MS studied with benzo[a]pyrene and isocyanates

This thesis focuses on methods for quantification by liquid chromatography/mass spectrometry (LC/MS) of specific biomarkers for internal dose of chemicals which induce toxicity through their electrophilic reactivity. In vivo such compounds are short-lived, and could feasibly be measured as their reaction products (adducts) with biomacromolecules. Analysis by MS methods of stable adducts offers the specificity and accuracy required to generate data on internal dose useful in risk estimation. The primary aim was to develop a method for quantification by LC/MS of bulky adducts to serum albumin (SA) from polycyclic aromatic hydrocarbons, using the genotoxic diolepoxide (DE) of benzo[a]pyrene (BP) as a model. A method for analysis of the BPDE adducts to His146 in SA was developed which is robust, easy-to-use, has good reproducibility and which reached a high sensitivity. A method for quantification of BPDE adducts to N2-deoxyguanosine (dG) in DNA by LC/MS was also established. In mice exposed to BP, adducts to SA and DNA from stereoisomers of BPDE were identified and quantified. The adduct level was shown to be &gt;400 times higher in DNA than in SA, which from an in vitro study could be concluded to mainly depend on a large difference in the rates of adduct formation to His in SA and to dG in DNA. BPDE adduct levels to SA and DNA, and a biomarker of genotoxic effect (frequency of micronuclei), were compared in BP-exposed mice. The results were used to evaluate how these methods could be used in procedures for cancer risk estimation. An LC/MS method for analysis of valine hydantoins (VH) formed as adducts from isocyanates to N-termini in haemoglobin was established. VH, formed from urea/isocyanic acid, was investigated in mice as a potential biomarker of renal failure and for dose adjustment during treatment with a radioactive cytostatic drug. The kidney dysfunction was not severe enough to give a significant increase of VH in the experiment. At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Manuscript.</p

Biomarkers of internal exposure/dose : Methods to quantify adducts to protein and DNA by LC/MS studied with benzo[a]pyrene and isocyanates

This thesis focuses on methods for quantification by liquid chromatography/mass spectrometry (LC/MS) of specific biomarkers for internal dose of chemicals which induce toxicity through their electrophilic reactivity. In vivo such compounds are short-lived, and could feasibly be measured as their reaction products (adducts) with biomacromolecules. Analysis by MS methods of stable adducts offers the specificity and accuracy required to generate data on internal dose useful in risk estimation. The primary aim was to develop a method for quantification by LC/MS of bulky adducts to serum albumin (SA) from polycyclic aromatic hydrocarbons, using the genotoxic diolepoxide (DE) of benzo[a]pyrene (BP) as a model. A method for analysis of the BPDE adducts to His146 in SA was developed which is robust, easy-to-use, has good reproducibility and which reached a high sensitivity. A method for quantification of BPDE adducts to N2-deoxyguanosine (dG) in DNA by LC/MS was also established. In mice exposed to BP, adducts to SA and DNA from stereoisomers of BPDE were identified and quantified. The adduct level was shown to be &gt;400 times higher in DNA than in SA, which from an in vitro study could be concluded to mainly depend on a large difference in the rates of adduct formation to His in SA and to dG in DNA. BPDE adduct levels to SA and DNA, and a biomarker of genotoxic effect (frequency of micronuclei), were compared in BP-exposed mice. The results were used to evaluate how these methods could be used in procedures for cancer risk estimation. An LC/MS method for analysis of valine hydantoins (VH) formed as adducts from isocyanates to N-termini in haemoglobin was established. VH, formed from urea/isocyanic acid, was investigated in mice as a potential biomarker of renal failure and for dose adjustment during treatment with a radioactive cytostatic drug. The kidney dysfunction was not severe enough to give a significant increase of VH in the experiment. At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Manuscript.</p

Ljud som samarbetspartners : En intra-aktiv studie om yngre barns ljudutforskande i förskolan

The purpose of this study is to examine children's intra-active relations with sounds in an explorative work at a preschool (1-to 2-year old children) analyzed through the lens of agential realism (Barad 2007, 2008), and to examine its didactical effects. This study has a transdisciplinary and cross-disciplinary design based on preschool didactics and the natural sciences, mainly physics andbiology. Research data consist of pedagogical documen-tation in the form of a short video sequence generated in a preschool sound project. An agential realistic approach in this study means an analysis of how sound is produced intra-actively in children's play and exploration in a pre-school. Barad’s agential realism also defines specific ethical stances for both the researcher’s involvement in the production of knowledge and the ethical implications of what that new knowledge and reality reveals(Barad 2007, 2008). The results of this study demonstrate the possibility to work with young preschool children around sound and how sound can be understood as a significant partner in children's play and exploration. This work ́s transdis-ciplinary goal, which is to work across the boundaries of preschool practice and scientific theory, contributes new knowledge about how sound vibration, frequency, loudness, hearingand acoustics intra-acts with children ́sbodies, feelings and thoughtsand the educational environmentsand discourses that children face in preschool. This study's specific impact on practice is that preschool staff can gain a greater understanding on the significance and im-pact of furnishings, architecture and organization according to time and place on how children express themselves and explore sound as a material-discursive phenomenon

What influences listed companies to disclose CSR informationon Facebook?

Begreppet Corporate Social Responsibility (CSR) är viktigt för både företag och samhället idag. För att uppnå legitimitet bör företag visa att de engagerar sig i CSR-frågor. En kanal som de kan använda för att kommunicera CSR är sociala nätverk, som vuxit sig stora de senaste åren. Företags CSR-upplysningar på sociala nätverk har dock inte utforskats i en svensk kontext tidigare. Denna studie ämnar därför bidra med ökad kunskap genom att undersöka CSR-upplysningar på det största sociala nätverket; Facebook.  Syftet med denna studie är att förklara vad som påverkar svenska börsnoterade bolag att ge ut CSR-upplysningar på Facebook. Uppsatsen utgår från en deduktiv ansats, där hypoteser har utvecklats med hjälp av ekonomiska och systemorienterade teorier samt tidigare forskning. Genom en tvärsnittsdesign har sedan kvantitativa sekundärdata i form av företags Facebookinlägg liksom ekonomisk information samlats in och analyserats med hjälp av en innehållsanalys. Studiens resultat visar att det finns ett antal faktorer som påverkar mängden CSR-upplysningar företag ger ut på Facebook. Företagsstorlek, koncentrerat ägande och branschtillhörighet är de faktorer som uppvisar signifikanta samband med den beroende variabeln Antal CSR-inlägg. Ju större ett företag är och ju mindre koncentrerat ägande det har, desto mer CSR-upplysningar ges ut på deras Facebooksida. Dessutom påvisas att företag i branscherna Konsumtionsvaror och Konsumtionstjänster ger ut mindre CSR-information på Facebook än IT-företag.Today, corporate social responsibility (CSR) is an important concept to society and corporations alike. To achieve legitimacy from society and its stakeholders, it is important for corporations to be able to show what CSR efforts they are making. There are multiple channels a corporation can choose from to communicate such matters, one of which is social media, a platform that has grown extensively over the last few years. Corporations’ CSR disclosures on social media has not been researched in a Swedish context before, which this study attempts to remedy by analysing the largest social media platform; Facebook. The purpose of this study is to explain what influences Swedish listed corporations' CSR disclosures on Facebook. With the help of economic and system-oriented theories as well as earlier research, hypotheses are constructed with a deductive approach. Quantitative secondary data in the form of companies’ Facebook entries and economical information is then collected through a cross-sectional design and analysed through content analysis. The results of the study show that company size, concentrated ownership and industry influence corporations’ CSR disclosures on Facebook. Consequently, bigger companies and companies with dispersed ownership disclose more CSR information on Facebook than smaller companies and companies with concentrated ownership. Also, companies in consumer goods and services disclose less CSR information than IT companies

What influences listed companies to disclose CSR informationon Facebook?

Begreppet Corporate Social Responsibility (CSR) är viktigt för både företag och samhället idag. För att uppnå legitimitet bör företag visa att de engagerar sig i CSR-frågor. En kanal som de kan använda för att kommunicera CSR är sociala nätverk, som vuxit sig stora de senaste åren. Företags CSR-upplysningar på sociala nätverk har dock inte utforskats i en svensk kontext tidigare. Denna studie ämnar därför bidra med ökad kunskap genom att undersöka CSR-upplysningar på det största sociala nätverket; Facebook.  Syftet med denna studie är att förklara vad som påverkar svenska börsnoterade bolag att ge ut CSR-upplysningar på Facebook. Uppsatsen utgår från en deduktiv ansats, där hypoteser har utvecklats med hjälp av ekonomiska och systemorienterade teorier samt tidigare forskning. Genom en tvärsnittsdesign har sedan kvantitativa sekundärdata i form av företags Facebookinlägg liksom ekonomisk information samlats in och analyserats med hjälp av en innehållsanalys. Studiens resultat visar att det finns ett antal faktorer som påverkar mängden CSR-upplysningar företag ger ut på Facebook. Företagsstorlek, koncentrerat ägande och branschtillhörighet är de faktorer som uppvisar signifikanta samband med den beroende variabeln Antal CSR-inlägg. Ju större ett företag är och ju mindre koncentrerat ägande det har, desto mer CSR-upplysningar ges ut på deras Facebooksida. Dessutom påvisas att företag i branscherna Konsumtionsvaror och Konsumtionstjänster ger ut mindre CSR-information på Facebook än IT-företag.Today, corporate social responsibility (CSR) is an important concept to society and corporations alike. To achieve legitimacy from society and its stakeholders, it is important for corporations to be able to show what CSR efforts they are making. There are multiple channels a corporation can choose from to communicate such matters, one of which is social media, a platform that has grown extensively over the last few years. Corporations’ CSR disclosures on social media has not been researched in a Swedish context before, which this study attempts to remedy by analysing the largest social media platform; Facebook. The purpose of this study is to explain what influences Swedish listed corporations' CSR disclosures on Facebook. With the help of economic and system-oriented theories as well as earlier research, hypotheses are constructed with a deductive approach. Quantitative secondary data in the form of companies’ Facebook entries and economical information is then collected through a cross-sectional design and analysed through content analysis. The results of the study show that company size, concentrated ownership and industry influence corporations’ CSR disclosures on Facebook. Consequently, bigger companies and companies with dispersed ownership disclose more CSR information on Facebook than smaller companies and companies with concentrated ownership. Also, companies in consumer goods and services disclose less CSR information than IT companies

What influences listed companies to disclose CSR informationon Facebook?

Begreppet Corporate Social Responsibility (CSR) är viktigt för både företag och samhället idag. För att uppnå legitimitet bör företag visa att de engagerar sig i CSR-frågor. En kanal som de kan använda för att kommunicera CSR är sociala nätverk, som vuxit sig stora de senaste åren. Företags CSR-upplysningar på sociala nätverk har dock inte utforskats i en svensk kontext tidigare. Denna studie ämnar därför bidra med ökad kunskap genom att undersöka CSR-upplysningar på det största sociala nätverket; Facebook.  Syftet med denna studie är att förklara vad som påverkar svenska börsnoterade bolag att ge ut CSR-upplysningar på Facebook. Uppsatsen utgår från en deduktiv ansats, där hypoteser har utvecklats med hjälp av ekonomiska och systemorienterade teorier samt tidigare forskning. Genom en tvärsnittsdesign har sedan kvantitativa sekundärdata i form av företags Facebookinlägg liksom ekonomisk information samlats in och analyserats med hjälp av en innehållsanalys. Studiens resultat visar att det finns ett antal faktorer som påverkar mängden CSR-upplysningar företag ger ut på Facebook. Företagsstorlek, koncentrerat ägande och branschtillhörighet är de faktorer som uppvisar signifikanta samband med den beroende variabeln Antal CSR-inlägg. Ju större ett företag är och ju mindre koncentrerat ägande det har, desto mer CSR-upplysningar ges ut på deras Facebooksida. Dessutom påvisas att företag i branscherna Konsumtionsvaror och Konsumtionstjänster ger ut mindre CSR-information på Facebook än IT-företag.Today, corporate social responsibility (CSR) is an important concept to society and corporations alike. To achieve legitimacy from society and its stakeholders, it is important for corporations to be able to show what CSR efforts they are making. There are multiple channels a corporation can choose from to communicate such matters, one of which is social media, a platform that has grown extensively over the last few years. Corporations’ CSR disclosures on social media has not been researched in a Swedish context before, which this study attempts to remedy by analysing the largest social media platform; Facebook. The purpose of this study is to explain what influences Swedish listed corporations' CSR disclosures on Facebook. With the help of economic and system-oriented theories as well as earlier research, hypotheses are constructed with a deductive approach. Quantitative secondary data in the form of companies’ Facebook entries and economical information is then collected through a cross-sectional design and analysed through content analysis. The results of the study show that company size, concentrated ownership and industry influence corporations’ CSR disclosures on Facebook. Consequently, bigger companies and companies with dispersed ownership disclose more CSR information on Facebook than smaller companies and companies with concentrated ownership. Also, companies in consumer goods and services disclose less CSR information than IT companies

Self-declarations of environmental classification at Fass.se

Since 2005 Sweden has a unique environmental classification system for pharmaceutical products. It is a self-declaration system where each pharmaceutical company is responsible for their own environmental information. The environmental risk assessments are published on the web based portal www.Fass.se, which is open to the public. Prior to publication the environmental risk assessments are reviewed by IVL as an independent, external part to make sure that the classifications are based on a scientifically acceptable interpretation of the guidance for the pharmaceutical companies. The present report describes the experiences from the review process during the year 2016. Data for the statistical analyses are gained both from the Fass.se database and from the “progression list”, a spreadsheet the audit team uses to keep track of documents that have been reviewed or are under current review. In 2016, 450 environmental risk assessments were sent in for review. Of these 48% received the comment no remarks and were recommended to be published. 27% received the assessment remark and were recommended to be corrected before publication and 26% needed to be corrected and sent in for another review before publication. The total number of unique substances that were published at Fass.se during 2016 was 371. Of these 26% were classified regarding environmental risk, 34% were exempted from classification and 40% were reviewed, but no classification could be made due to lack of data. Of the classified substances 82% received the assessment insignificant risk. No substance was classified as posing high risk or being hazardous. Two substances (Estradiol and Terbinafine), published during 2016, were classified as posing a moderate risk. 60% of the unique substances were assessed for bioaccumulation potential but 90% of these were classified with low potential for bioaccumulation. 31% of the unique substances were assessed for degradation and 73% of these were classified as potentially persistent. The work of improving the review system is an on-going process. As a part of this work IVL Swedish Environmental Research Institute performs studies and activities to increase the knowledge of pharmaceuticals in the environment. During 2016 IVL organized a Dialogue meeting, “10 years of environmental classification of pharmaceuticals at Fass.se”, with representatives from administrative authorities, industry, stakeholders and scientists in order to present and discuss the work with environmental classification of pharmaceuticals (Graae et al. 2017). In addition, experiences from the reviewing process of the self-declaration system of environmental classification of pharmaceuticals at Fass.se were summarized and evaluated in a peer-reviewed article (Magnér et al. 2017).Since 2005 Sweden has a unique environmental classification system for pharmaceutical products. It is a self-declaration system where each pharmaceutical company is responsible for their own environmental information. The environmental risk assessments are published on the web based portal www.Fass.se, which is open to the public. Prior to publication the environmental risk assessments are reviewed by IVL as an independent, external part to make sure that the classifications are based on a scientifically acceptable interpretation of the guidance for the pharmaceutical companies. The present report describes the experiences from the review process during the year 2016. Data for the statistical analyses are gained both from the Fass.se database and from the “progression list”, a spreadsheet the audit team uses to keep track of documents that have been reviewed or are under current review. In 2016, 450 environmental risk assessments were sent in for review. Of these 48% received the comment no remarks and were recommended to be published. 27% received the assessment remark and were recommended to be corrected before publication and 26% needed to be corrected and sent in for another review before publication. The total number of unique substances that were published at Fass.se during 2016 was 371. Of these 26% were classified regarding environmental risk, 34% were exempted from classification and 40% were reviewed, but no classification could be made due to lack of data. Of the classified substances 82% received the assessment insignificant risk. No substance was classified as posing high risk or being hazardous. Two substances (Estradiol and Terbinafine), published during 2016, were classified as posing a moderate risk. 60% of the unique substances were assessed for bioaccumulation potential but 90% of these were classified with low potential for bioaccumulation. 31% of the unique substances were assessed for degradation and 73% of these were classified as potentially persistent. The work of improving the review system is an on-going process. As a part of this work IVL Swedish Environmental Research Institute performs studies and activities to increase the knowledge of pharmaceuticals in the environment. During 2016 IVL organized a Dialogue meeting, “10 years of environmental classification of pharmaceuticals at Fass.se”, with representatives from administrative authorities, industry, stakeholders and scientists in order to present and discuss the work with environmental classification of pharmaceuticals (Graae et al. 2017). In addition, experiences from the reviewing process of the self-declaration system of environmental classification of pharmaceuticals at Fass.se were summarized and evaluated in a peer-reviewed article (Magnér et al. 2017).IVL has since 2005, with the launch of the system of self-declarations of environmental classification at www.Fass.se, conducted a project focused on review of the self-declarations financed by LIF .This report describes the experiences gained during the review process in year 2016 and has been prepared with the aim to achieve transparency by explaining the role and the experiences of the reviewer, which may be useful in future development of the system. Den här rapporten finns endast på engelska. Svensk sammanfattning finns i rapporten

Self-declarations of environmental classification at Fass.se

Since 2005 Sweden has a unique environmental classification system for pharmaceutical products. It is a self-declaration system where each pharmaceutical company is responsible for their own environmental information. The environmental risk assessments are published on the web based portal www.Fass.se, which is open to the public. Prior to publication the environmental risk assessments are reviewed by IVL as an independent, external part to make sure that the classifications are based on a scientifically acceptable interpretation of the guidance for the pharmaceutical companies. The present report describes the experiences from the review process during the year 2016. Data for the statistical analyses are gained both from the Fass.se database and from the “progression list”, a spreadsheet the audit team uses to keep track of documents that have been reviewed or are under current review. In 2016, 450 environmental risk assessments were sent in for review. Of these 48% received the comment no remarks and were recommended to be published. 27% received the assessment remark and were recommended to be corrected before publication and 26% needed to be corrected and sent in for another review before publication. The total number of unique substances that were published at Fass.se during 2016 was 371. Of these 26% were classified regarding environmental risk, 34% were exempted from classification and 40% were reviewed, but no classification could be made due to lack of data. Of the classified substances 82% received the assessment insignificant risk. No substance was classified as posing high risk or being hazardous. Two substances (Estradiol and Terbinafine), published during 2016, were classified as posing a moderate risk. 60% of the unique substances were assessed for bioaccumulation potential but 90% of these were classified with low potential for bioaccumulation. 31% of the unique substances were assessed for degradation and 73% of these were classified as potentially persistent. The work of improving the review system is an on-going process. As a part of this work IVL Swedish Environmental Research Institute performs studies and activities to increase the knowledge of pharmaceuticals in the environment. During 2016 IVL organized a Dialogue meeting, “10 years of environmental classification of pharmaceuticals at Fass.se”, with representatives from administrative authorities, industry, stakeholders and scientists in order to present and discuss the work with environmental classification of pharmaceuticals (Graae et al. 2017). In addition, experiences from the reviewing process of the self-declaration system of environmental classification of pharmaceuticals at Fass.se were summarized and evaluated in a peer-reviewed article (Magnér et al. 2017).Since 2005 Sweden has a unique environmental classification system for pharmaceutical products. It is a self-declaration system where each pharmaceutical company is responsible for their own environmental information. The environmental risk assessments are published on the web based portal www.Fass.se, which is open to the public. Prior to publication the environmental risk assessments are reviewed by IVL as an independent, external part to make sure that the classifications are based on a scientifically acceptable interpretation of the guidance for the pharmaceutical companies. The present report describes the experiences from the review process during the year 2016. Data for the statistical analyses are gained both from the Fass.se database and from the “progression list”, a spreadsheet the audit team uses to keep track of documents that have been reviewed or are under current review. In 2016, 450 environmental risk assessments were sent in for review. Of these 48% received the comment no remarks and were recommended to be published. 27% received the assessment remark and were recommended to be corrected before publication and 26% needed to be corrected and sent in for another review before publication. The total number of unique substances that were published at Fass.se during 2016 was 371. Of these 26% were classified regarding environmental risk, 34% were exempted from classification and 40% were reviewed, but no classification could be made due to lack of data. Of the classified substances 82% received the assessment insignificant risk. No substance was classified as posing high risk or being hazardous. Two substances (Estradiol and Terbinafine), published during 2016, were classified as posing a moderate risk. 60% of the unique substances were assessed for bioaccumulation potential but 90% of these were classified with low potential for bioaccumulation. 31% of the unique substances were assessed for degradation and 73% of these were classified as potentially persistent. The work of improving the review system is an on-going process. As a part of this work IVL Swedish Environmental Research Institute performs studies and activities to increase the knowledge of pharmaceuticals in the environment. During 2016 IVL organized a Dialogue meeting, “10 years of environmental classification of pharmaceuticals at Fass.se”, with representatives from administrative authorities, industry, stakeholders and scientists in order to present and discuss the work with environmental classification of pharmaceuticals (Graae et al. 2017). In addition, experiences from the reviewing process of the self-declaration system of environmental classification of pharmaceuticals at Fass.se were summarized and evaluated in a peer-reviewed article (Magnér et al. 2017).IVL has since 2005, with the launch of the system of self-declarations of environmental classification at www.Fass.se, conducted a project focused on review of the self-declarations financed by LIF .This report describes the experiences gained during the review process in year 2016 and has been prepared with the aim to achieve transparency by explaining the role and the experiences of the reviewer, which may be useful in future development of the system. Den här rapporten finns endast på engelska. Svensk sammanfattning finns i rapporten