The plasma inorganic phosphate level may be influenced by (1) factors affecting the intermediary metabolism of phosphorus, (2) alternation in the degree of absorption of phosphorus, (3) alteration in the degree of excretion of phosphorus. In the introduction, the intermediary metabolism of phosphorus, particularly as far as the endocrine glands are concerned, is discussed in detail, whereas the absorption and excretion are but briefly outlined.

It is fundamental to investigate the biodegradability of chemicals and their potential (eco)toxicological effects under near-environmental conditions in order to identify and thereby avoid potential risks to humans, animals and the environment in the event of their release. Established as a policy object at the European level, the risks, which are posed by anthropogenic pollution, ideally need to be reduced to a minimum, if not eliminated completely, in the near future. To achieve this goal, an assessment of chemicals, based on international consensus, is required, which builds on the results of standardized experiments and is constantly supplemented by computer-based approaches. Establishing structure-property relationships is one way to immediately classify organic trace substances as ‘degradable’, or ‘potentially persistent’, as well as as hormonally ‘active’ or ‘inactive’. The extent to which these relationships are applicable to the substance group of benzophenone-type UV filters was investigated in this work. Some derivatives, which only differ in the type and position of their substituents on the aromatic rings, are suspected of acting as endocrine disruptors. Despite the high probability of them being released into the environment, and the toxicologically relevant properties, there are no mechanistic degradation studies so far that take enough derivatives into consideration to discuss the substitution pattern as a possible influential factor. To close the identified gaps, experiments on primary as well as ultimate degradation were carried out with up to ten different benzophenones, changing various parameters and adapting the experimental setup. Studies on the complete mineralizability, compliant with the standardized OECD Guideline No. 301F, showed that the respective substitution pattern is a decisive factor, while the mere presence of certain functional groups plays a minor role. To yield additional information on the time-dependent formation of primary degradation products, an LC-MS/MS method was developed that served to quantify benzophenones in various environmental matrices during a monitoring campaign, in addition to tracking primary degradation at the laboratory scale. The detection of 4-hydroxybenzophenone, which meets the structural criteria for multi-hormonal effects and was identified as a microbial degradation product of benzophenone, confirmed that the formation of transformation products needs to be given greater consideration in relation to toxicological issues. On this evidence, the structure-dependent endocrine effects of benzophenone-type UV filters, the transformation product 4-hydroxybenzophenone, and three other degradation products were determined using recombinant yeast-based reporter gene assays. Hydroxyl groups are the prevalent substituents of benzophenone-type UV filters, and the ruling structural elements, which influence microbial biodegradation and endocrine activity. Their investigation revealed a new fundamental but unexpected relationship: Primary degradation can slow down further degradation through the incorporation of hydroxyl groups. This simultaneously increases the risk of a formation of estrogen-active transformation products. This aspect underlines the need to include the occurrence of transformation products, especially under realistic conditions, in the overall risk assessment of chemicals. In this context, the application of quantitative structure-activity relationships (QSAR) plays a crucial role and, the suitability thereof was verified in this work – focusing on benzophenones. The empirically proven relationship between substitution pattern and degradability helps to improve the reliability of QSAR models for benzophenones as well as for structurally similar compounds, and forms the basis for further studies of this specific relationship at the enzymatic level.:DECLARATION OF CONFORMITY DECLARATION OF INDEPENDENT WORK PREFACE ACKNOWLEDGMENT KURZFASSUNG ABSTRACT LIST OF ABBREVIATIONS AND ACRONYMS 1 CONTEXTUAL FRAMEWORK AND OBJECTIVES 2 STATE OF KNOWLEDGE ABOUT THE BIODEGRADATION OF BENZOPHENONES 2.1 INTRODUCTION 2.2 ENTRY PATHS INTO THE ENVIRONMENT AND HAZARDOUS EFFECTS 2.2.1 Environmental occurrence and possible routes of discharge 2.2.2 (Eco)toxicity and endocrine disrupting properties 2.3 BIODEGRADATION 2.3.1 Aerobic biotransformation 2.3.2 Anoxic/anaerobic biotransformation 2.3.3 Transformation mediated through fungi and higher organisms 2.4 PHOTOLYTIC TRANSFORMATION 2.5 CONCLUSIONS 3 TRACE ANALYSIS IN ENVIRONMENTAL SAMPLES AND THE ENDOCRINE EFFECTS 3.1 INTRODUCTION 3.2 MATERIAL AND METHODS 3.2.1 Chemicals and materials 3.2.2 LC-MS/MS method development 3.2.2.1 MS parameters 3.2.2.2 LC parameters 3.2.2.3 Sample preparation 3.2.2.4 Validation 3.2.2.5 Application of the method to environmental monitoring 3.2.3 Biodegradation 3.2.4 Yeast-based reporter gene assays 3.3 RESULTS AND DISCUSSION 3.3.1 LC-MS/MS method development 3.3.1.1 Sample preparation 3.3.1.2 Validation 3.3.1.3 Application of the method for environmental samples 3.3.2 Biodegradation 3.3.3 Endocrine activity 3.3.3.1 Estrogenic and antiestrogenic activities 3.3.3.2 Estrogenic activity during biotransformation 3.3.3.3 Androgenic and antiandrogenic activities 3.4 CONCLUSION 4 PRIMARY AND ULTIMATE DEGRADATION 4.1 INTRODUCTION 4.2 MATERIAL AND METHODS 4.2.1 Chemicals and materials 4.2.2 Primary degradation 4.2.2.1 Abiotic river water 4.2.2.2 Biotic river water 4.2.2.3 Suboxic river water 4.2.2.4 River water amended with mineral solution 4.2.3 Ready biodegradability 4.2.4 Column experiments 4.2.5 Docking studies 4.2.6 LC-MS/MS Analysis 4.3 RESULTS AND DISCUSSION 4.3.1 Primary degradation 4.3.1.1 Abiotic river water 4.3.1.2 Biotic river water 4.3.1.3 Suboxic river water 4.3.1.4 River water amended with mineral solution 4.3.2 Ready biodegradability 4.3.3 Column experiments 4.3.3.1 Breakthrough curves and pretests 4.3.3.2 Removal tests 4.3.4 Structure-biodegradability relationships 4.4 CONCLUSIONS 5 SYNTHESIS 5.1 SUMMARIZING DISCUSSION 5.2 COMPARISON TO IN SILICO RESULTS 5.2.1 Biodegradability 5.2.2 Estrogenicity 5.3 CONCLUSION 6 APPENDIX 6.1 APPENDIX A 6.2 APPENDIX B 6.3 APPENDIX C 6.4 APPENDIX D 7 REFERENCES