| Abstract | 第6-7页 |
| 摘要 | 第8-17页 |
| List of Abbreviations | 第17-21页 |
| Chapter 1 Introduction and literature review | 第21-49页 |
| 1.1 General introduction | 第21-43页 |
| 1.1.1 Existing regulations for priority substances (PSs) and contaminants of emergingconcerns (CECs) | 第21-24页 |
| 1.1.2 Sources of DEHP, PAHs, and PPCPs | 第24-25页 |
| 1.1.3 Occurrence of PAHs, DEHP, and PPCPs in surface water | 第25-35页 |
| 1.1.4 Ecological risks of PAHs, DEHP, and PPCPs | 第35-36页 |
| 1.1.5 Preferred extraction and quantification techniques | 第36-37页 |
| 1.1.6 Potential toxicity of DEHP, PAHs, and PPCPs | 第37-43页 |
| 1.2 Zebrafish as an animal model | 第43-44页 |
| 1.3 Objectives and rationale of the study | 第44-47页 |
| 1.4 Graphical layout of the study | 第47-49页 |
| Chapter 2 Materials and methods | 第49-65页 |
| 2.1 Environmental analysis and ecological risk assessment (ERA) | 第49-57页 |
| 2.1.1 Selection of the sites, surface water sampling, and characterization | 第49-51页 |
| 2.1.2 Surface water sample extraction and GC-MS analysis | 第51-52页 |
| 2.1.3 Quality control and quality assurance (QC/QA) | 第52-54页 |
| 2.1.4 Methods for ecological risk assessment (ERA) | 第54-57页 |
| 2.2 Methods for in vivo toxicity assessment | 第57-60页 |
| 2.2.1 Ethical statement and Zebrafish fish husbandry | 第57页 |
| 2.2.2 PAHs toxicity evaluation after exposure to surface water in wild-type andtransgenic zebrafish embryos | 第57-58页 |
| 2.2.3 Acute and chronic exposure to DEHP in zebrafish | 第58页 |
| 2.2.4 Exposure to PPCP and developmental indices analysis in zebrafish | 第58页 |
| 2.2.5 Responses of developmental markers after exposure to PPCPs using in situhybridization | 第58-59页 |
| 2.2.6 RNAs extraction and Quantitative real-time PCR (qRT-PCR) | 第59页 |
| 2.2.7 AhR activity analysis using Tg(cypla:gfp/mCherry) zebrafish | 第59-60页 |
| 2.3 Methods for in vitro toxicity assessment | 第60-62页 |
| 2.3.1 Cell culture and cell viability analysis after DEHP and PPCPs exposure | 第60页 |
| 2.3.2 Comet assay after DEHP and PPCPs exposure | 第60-61页 |
| 2.3.4 qRT-PCR analysis in HEK293T cells after PPCPs exposure | 第61-62页 |
| 2.3.5 Cancer cells transfection in zebrafish after DEHP exposure | 第62页 |
| 2.4 Bioactivity profiles and toxicity estimation of PPCPs | 第62-63页 |
| 2.5 Gene interaction network construction for PPCPs metabolism | 第63页 |
| 2.6 Statistical analysis | 第63页 |
| 2.7 Chemicals | 第63-65页 |
| Chapter 3 Environmental concerns and toxicogenetic endpoints of DEHP | 第65-87页 |
| 3.1 Introduction | 第65-66页 |
| 3.2 Environmental concerns of DEHP in the TGRA | 第66-74页 |
| 3.2.1 Environmental levels and spatial distribution of DEHP in the TGRA | 第66-68页 |
| 3.2.2 Ecological risk assessment (ERA) of DEHP in the TGRA | 第68-74页 |
| 3.3 In vitro toxicity of DEHP | 第74-80页 |
| 3.3.1 Cell viability and DNA damage to the human breast carcinoma cells | 第74-77页 |
| 3.3.2 DEHP exposure activates the migration of human breast carcinoma cells inzebrafish | 第77-80页 |
| 3.4 In vivo toxicity of DEHP | 第80-86页 |
| 3.4.1 Acute exposure to DEHP at ERCs activates the pi3k-akt-mTOR pathway inzebrafish | 第80页 |
| 3.4.2 Chronic exposure to DEHP suppresses the HPT axis pathway in adult zebrafish | 第80-84页 |
| 3.4.3 DEHP induces AhR activity in Tg(cypla:gfp) zebrafish | 第84-86页 |
| Conclusion | 第86-87页 |
| Chapter 4 Environmental concerns and toxicogenetic endpoints of PAHs | 第87-115页 |
| 4.1 Introduction | 第87-88页 |
| 4.2 Environmental concerns of PAHs | 第88-102页 |
| 4.2.1 Environmental levels and spatial distribution of PAHs in the TGRA | 第88-93页 |
| 4.2.2 Tracking compositional pattern of PAHs | 第93-96页 |
| 4.2.3 Ecological risk assessment (ERA) of PAHs | 第96-102页 |
| 4.3 PAHs associated genotoxicity in zebrafish | 第102-110页 |
| 4.3.1 Toxicity scenario of ∑PAHs in the TGRA | 第102-107页 |
| 4.3.2 Individual PAHs toxicity scenario in the TGRA | 第107-110页 |
| 4.4 Response of Tg(cypl a:gfp) zebrafish to TGRA surface water | 第110-112页 |
| 4.5 PAHs mediated AhR activity in Tg(cypl a: mCherry) zebrafish | 第112-114页 |
| Conclusion | 第114-115页 |
| Chapter 5 Environmental concerns and toxicogenetic endpoints of PPCPs | 第115-161页 |
| 5.1 Introduction | 第115-117页 |
| 5.2 Ranking PPCPs using ToxCast bioactivity and primary toxicity endpoints | 第117-121页 |
| 5.3 Prioritizing PPCPs based on environmental concerns in TGRA | 第121-129页 |
| 5.4 Prioritizing PPCPs using in vitro toxicity assays | 第129-136页 |
| 5.4.1 Cell viability and DNA damage in HEK293T cells | 第129-133页 |
| 5.4.2 Response of pi3k-akt-mTOR pathway in HEK293T cells | 第133-136页 |
| 5.5 Prioritizing PPCPs using in vivo toxicity assays | 第136-159页 |
| 5.5.1 Developmental toxicity in zebrafish | 第136-139页 |
| 5.5.2 Responses of muscle, blood, and liver developmental markers | 第139-142页 |
| 5.5.3 PPCPs metabolism in zebrafish | 第142-147页 |
| 5.5.4 Interactions among genetic markers of phase Ⅰ, Ⅱ, and Ⅲ pathway for PPCPsmetabolism/detoxification | 第147-153页 |
| 5.5.5 Effect of PPCPs metabolism on zebrafish development | 第153-157页 |
| 5.5.6 Responses of Tg(cypla:mCherry) zebrafish to PPCPs (AhR activity) | 第157-159页 |
| Conclusion | 第159-161页 |
| Chapter 6 Innovative findings and research outlook | 第161-166页 |
| 6.1 Innovative findings | 第161-164页 |
| 6.2 Research outlook | 第164-166页 |
| References | 第166-200页 |
| Appendix | 第200-222页 |
| Appendices A | 第200-206页 |
| Appendices B | 第206-211页 |
| Appendix C | 第211-222页 |
| Acknowledgement | 第222-224页 |
| Resume and publications | 第224-225页 |
