Kühnert A. Time course analyses for understanding internal exposure and toxicokinetic processes in fish embryos: Diss. … Dr. der Naturwiss. / Helmholtz centre for environmental research - UFZ (Leipzig). - Leipzig: Helmholtz centre for environmental research - UFZ, 2016. - xiv, 101 p.: ill., tab. - (PhD Dissertation; 01/2016). - Res. also Germ. - Bibliogr.: p.86-91. - ISSN 1860-0387 Шифр: (Pr 1117/2016-1) 02  Место хранения:   02 | Отделение ГПНТБ СО РАН | Новосибирск

Оглавление / Contents

List of Figures ................................................. X List of Tables ................................................. XI Abbreviations ................................................. XII 1 General Introduction ....................................... 1 1.1 EXPOSURE AND EFFECT-RELATIONSHIPS IN ECOTOXICOLOGICAL CONTEXT .................................................... 1 1.2 NOMINAL, AMBIENT AND INTERNAL EXPOSURE CONCENTRATION AS DESCRIPTORS OF TOXICITY .................................... 3 1.3 FISH EMBRYOS IN ECOTOXICOLOGY .............................. 5 1.4 BIOTRANSFORMATION .......................................... 7 1.5 MIXTURE EXPOSURE .......................................... 10 2 The relationship between ambient and internal concentration time profiles a toxicokinetic approach using zebrafish (Danio rerio) embryos ..................... 11 2.1 HIGHLIGHTS ................................................ 12 2.2 INTRODUCTION .............................................. 12 2.3 MATERIALSAND METHODS ...................................... 15 2.3.1 Reagents ........................................... 15 2.3.2 Zebrafish maintenance, embryo collection and exposure conditions ................................ 16 2.3.3 Experimental set-up ................................ 16 2.3.4 Quantification of the ambient and internal concentration ...................................... 18 2.3.5 Toxicokinetic model ................................ 19 2.4 RESULTS AND DISCUSSION .................................... 20 2.4.1 Quantification of the ambient concentration ........ 20 2.4.2 Quantification of the internal concentration ....... 23 2.4.3 Comparison of ambient and internal concentration- time profiles ...................................... 26 2.4.4 Relevance for toxicity testing ..................... 29 3 Biotransformation in fish embryos - linking temporal gene expression patterns of Cyp enzymes to internal exposure dynamics after exposure with an AhR binding xenobiotic ................................................ 31 3.1 HIGHLIGHTS ................................................ 32 3.2 INTRODUCTION .............................................. 32 3.3 MATERIALS AND METHODS ..................................... 35 3.3.1 Reagents ............................................ 35 3.3.2 Danio rerio maintenance, embryo collection and exposure conditions ................................ 35 3.3.3 Experimental set-up ................................ 35 3.3.4 Chemical analyses .................................. 37 3.3.5 qPCR analysis ...................................... 38 3.4 RESULTS AND DISCUSSION ..................................... 39 3.4.1 Xenobiotic induced CYP gene expression in zebrafish embryos .................................. 39 3.4.2 Distinctive time profiles of ambient and internal exposure concentration ............................. 45 3.4.3 CYP mediated formation of BAA biotransformation products ........................................... 48 3.4.4 Temporal gene expression patterns drive the dynamics of internal exposure ...................... 49 4 Time course analysis reveals toxicokinetic interaction under mixture exposure .................................... 53 4.1 HIGHLIGHTS ................................................ 54 4.2 INTRODUCTION .............................................. 54 4.3 MATERIALS AND METHODS ..................................... 56 4.3.1 Reagents ........................................... 56 4.3.2 Danio rerio maintenance, embryo collection and exposure conditions ................................ 57 4.3.3 Experimental set-up ................................ 58 4.3.4 Chemical analyses .................................. 58 4.3.5 Toxicokinetic model ................................ 59 4.4 RESULTS ................................................... 61 4.4.1 Internal concentration-time profiles of 7 PAHs under mixture exposure ............................. 61 4.4.2 Mass balance calculations .......................... 63 4.4.3 Estimated toxicokinetic parameters of mixture exposure ........................................... 65 4.5 DISCUSSION ................................................ 69 4.5.1 Accumulation in fish embryos and toxicokinetic interactions with uptake and elimination ........... 70 4.5.2 Interaction with biotransformation processes ....... 73 5 General Conclusion ........................................ 77 6 Outlook ................................................... 83 7 References ................................................ 86 8 Annex ..................................................... 91