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Abstract
The rapid expansion of the nanotechnology field raises concerns, like any new technology, about the toxicity and environmental impact of nanomaterials. This book addresses the gaps relating to health and safety issues of this field and aims to bring together fragmented knowledge on nanosafety. Not only do chapters address conventional toxicity issues, but also more recent developments such as food borne nanoparticles, life cycle analysis of nanoparticles and nano ethics. In addition, the authors discuss the environmental impact of nanotechnologies as well as safety guidelines and ethical issues surrounding the use of nanoparticles. In particular this book presents a unique compilation of experimental and computational perspectives and illustrates the use of computational models as a support for experimental work. Nanotoxicology: Experimental and Computational Perspectives is aimed towards postgraduates, academics, and practicing industry professionals. This highly comprehensive review also serves as an excellent foundation for undergraduate students and researchers new to nanotechnology and nanotoxicology. It is of particular value to toxicologists working in nanotechnology, chemical risk assessment, food science, environmental, safety, chemical engineering, the biological sciences and pharmaceutical research.
Professor Alok Dhawan is currently the Director at the Institute of Life Sciences in Ahmedabad University, India, on lien from CSIR-Indian Institute of Toxicology Research, Lucknow where he is Principal Scientist and Area Coordinator for the Nanomaterial Toxicology Group. Professor Dhawan is one of the originators of nanomaterial toxicology research in India. He is a Series Editor for the Royal Society of Chemistry Issues in Toxicology series.
Professor Rishi Shanker is also based with the Institute of Life Sciences at Ahmedabad University. Previous to this he was Chief Scientist at the CSIR-Indian Institute of Toxicology Research in Lucknow and a Professor at the Academy for Scientific and Innovative Research. Dr. Shanker served as Area Coordinator of core research areas of ‘Environmental Toxicology’ and ‘Nanomaterial Toxicology’ at CSIR-IITR.
Both Professor Dhawan and Professor Shanker were instrumental in the development of the state of art ‘Environmental Biotechnology’ facility at CSIR-NEERI.
Professor Diana Anderson is a Professor of Biomedical Science and Established Chair at the Bradford School of Medical Sciences, UK and a Distinguished Professor at Ahmedabad University. Professor Anderson is a Series Editor for the Current Toxicology series published by John Wiley and Sons, and the Editor in Chief of the Royal Society of Chemistry Issues in Toxicology series.
The Editors have published prolifically in the field of nanotoxicology individually and collaboratively. They are amongst the founding members of the Indian Nanoscience Society which launched in 2007 and have contributed realty to initiating this discipline in India.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Cover | Cover | ||
| Foreword | vii | ||
| Preface | ix | ||
| Editor Biographies | xi | ||
| Contents | xv | ||
| Chapter 1 Nanotoxicology: Challenges for Biologists | 1 | ||
| 1.1 Introduction | 1 | ||
| 1.2 The Hurdles in Toxicity Evaluation of NMs | 2 | ||
| 1.3 ENM Interference with Toxicity Test Methods | 4 | ||
| 1.3.1 Interference of NPs with Metabolic Activity Detection Assays | 4 | ||
| 1.3.2 Interference of NPs in Assays for Cell Death Measurement | 5 | ||
| 1.3.3 Interference of ENPs with Immunoassays | 5 | ||
| 1.3.4 Interference of ENMs in Assays with Enzymes | 6 | ||
| 1.3.5 Interference with Measurement of Free Radicals Generated due to ENM Exposure | 6 | ||
| 1.3.6 Interference in Cellular Uptake Assays | 7 | ||
| 1.3.7 Interference with Cell Culture Media Components | 8 | ||
| 1.3.8 Interference due to Oxidation State Change in Redox-active ENMs | 9 | ||
| 1.3.9 Misinterpretation of TEM Images | 9 | ||
| 1.3.10 Interference with the Comet Assay | 10 | ||
| 1.3.11 Interference in Micronucleus Assays | 11 | ||
| 1.4 Conclusions | 11 | ||
| Acknowledgments | 12 | ||
| References | 12 | ||
| Chapter 2 Chemical Synthesis of Nanoparticles for Diverse Applications | 17 | ||
| 2.1 Introduction | 17 | ||
| 2.2 Synthesis of Metallic/Bimetallic Nanostructures | 19 | ||
| 2.2.1 Solvothermal Synthesis | 19 | ||
| 2.2.2 Reduction and Monolayer Capping in Aqueous and Non-aqueous Media | 21 | ||
| 2.2.3 Polymer-capped Metal Nanoparticles and Bimetallic Nanoclusters | 22 | ||
| 2.2.4 Synthesis in Microemulsion | 24 | ||
| 2.3 Synthesis of Polymer Nanoparticles | 25 | ||
| 2.3.1 Emulsification/Solvent Evaporation | 25 | ||
| 2.3.2 Chemical Precipitation/Nanoprecipitation | 27 | ||
| 2.4 Synthesis of Magnetic Nanoparticles | 27 | ||
| 2.4.1 Co-precipitation | 27 | ||
| 2.5 Conclusions | 28 | ||
| References | 29 | ||
| Chapter 3 Synthesis of Nanoparticles for Biomedical Applications | 39 | ||
| 3.1 Introduction | 39 | ||
| 3.2 Synthesis of Gold Nanoparticles | 40 | ||
| 3.2.1 Chemical Methods | 40 | ||
| 3.2.2 Physical Methods | 42 | ||
| 3.2.3 Biological Methods | 42 | ||
| 3.2.4 Biological Applications of Gold Nanoparticles | 43 | ||
| 3.3 Synthesis of Magnetic Nanoparticles | 46 | ||
| 3.3.1 Co-precipitation Method | 47 | ||
| 3.3.2 Microemulsion Method | 47 | ||
| 3.3.3 Sol-gel Method | 49 | ||
| 3.3.4 Sonochemical Method | 49 | ||
| 3.3.5 Flow Injection Method | 49 | ||
| 3.3.6 Hydrothermal Method | 50 | ||
| 3.3.7 Biological Applications of Magnetic Nanoparticles | 51 | ||
| 3.4 Synthesis of Carbon Nanotubes | 52 | ||
| 3.4.1 Arc Discharge Method | 53 | ||
| 3.4.2 Laser Ablation Method | 54 | ||
| 3.4.3 Chemical Vapour Deposition Method | 55 | ||
| 3.4.4 Biological Applications of CNTs | 56 | ||
| 3.5 Synthesis of Quantum Dots | 58 | ||
| 3.5.1 Biological Applications of Quantum Dots | 60 | ||
| 3.6 Synthesis of Silica Nanoparticles | 63 | ||
| 3.6.1 Stöber Method | 64 | ||
| 3.6.2 Microemulsion Method | 65 | ||
| 3.6.3 Biological Applications of Silica Nanoparticles | 66 | ||
| 3.7 Toxicity Considerations of Nanomaterials | 68 | ||
| 3.8 Conclusions | 69 | ||
| Acknowledgments | 70 | ||
| References | 70 | ||
| Chapter 4 Protocols for In vitro and In vivo Toxicity Assessment of Engineered Nanoparticles | 94 | ||
| 4.1 Introduction | 94 | ||
| 4.2 Cytotoxicity | 96 | ||
| 4.2.1 MTT Assay | 96 | ||
| 4.3 Live/Dead Assessment | 99 | ||
| 4.3.1 Propidium Iodide Uptake Assay | 99 | ||
| 4.3.2 Trypan Blue Exclusion Test | 101 | ||
| 4.4 Genotoxicity | 104 | ||
| 4.4.1 Single-cell Gel Electrophoresis Assay | 104 | ||
| 4.4.2 The CBMN Assay | 109 | ||
| 4.5 Immunotoxicity | 113 | ||
| 4.5.1 Cytokine Release | 113 | ||
| 4.5.2 Immunophenotyping | 115 | ||
| 4.6 Oxidative Stress | 119 | ||
| 4.6.1 ROS Generation | 119 | ||
| 4.6.2 Glutathione Estimation | 122 | ||
| 4.6.3 Lipid Peroxidation Determination | 126 | ||
| 4.7 Conclusions | 130 | ||
| Acknowledgments | 130 | ||
| References | 130 | ||
| Chapter 5 Nanoparticles in Biomedicine and Medicine, and Possible Clinical Toxicological Application of Peripheral Lymphocytes in the Risk Assessment Process for Susceptible Disease State Individuals | 133 | ||
| 5.1 Introduction | 133 | ||
| 5.2 Applications of Nanoparticles | 134 | ||
| 5.3 Nanoparticles in Biomedicine and Medicine | 135 | ||
| 5.4 Applications of Nanoparticles in Biomarker Detection | 136 | ||
| 5.5 Nanoparticle Toxicology | 136 | ||
| 5.6 Nanoparticle Toxicity in Human Cells and Individuals with Various Disease States Including Cancer | 137 | ||
| 5.6.1 Studies using Human Peripheral Lymphocytes in Clinical Toxicology Applications | 139 | ||
| 5.7 Conclusions | 146 | ||
| References | 148 | ||
| Chapter 6 Health Hazard and Risk Assessment of Nanoparticles Applied in Biomedicine | 151 | ||
| 6.1 Introduction | 151 | ||
| 6.2 Nanomaterials and Nanotechnology | 152 | ||
| 6.2.1 Nanomaterials | 152 | ||
| 6.2.2 Physicochemical Properties of NMs | 153 | ||
| 6.2.3 Nanomedicine | 155 | ||
| 6.2.4 Applications of Engineered NMs in Medicine | 156 | ||
| 6.3 Nanotoxicology | 158 | ||
| 6.3.1 Mechanisms of Toxicity | 158 | ||
| 6.3.2 Health Risks of NM Exposure | 162 | ||
| 6.3.3 Risk Assessment | 162 | ||
| 6.4 Nanomaterials in a Regulatory Perspective | 163 | ||
| 6.5 Conclusions | 164 | ||
| References | 165 | ||
| Chapter 7 Emerging Systems Toxicology Approaches in Nanosafety Assessment | 174 | ||
| 7.1 Introduction | 174 | ||
| 7.2 Omics: An Overview of Available Technologies | 175 | ||
| 7.2.1 Transcriptomics | 177 | ||
| 7.2.2 Proteomics | 178 | ||
| 7.2.3 Metabolomics and Lipidomics | 178 | ||
| 7.2.4 Genomics and Epigenomics | 183 | ||
| 7.2.5 Emerging Multiomics Studies | 185 | ||
| 7.3 Omics Applications in Nanotoxicological Research | 185 | ||
| 7.3.1 Mammalian In vitro Models for Omics | 187 | ||
| 7.3.2 Mammalian In vivo Models for Omics | 190 | ||
| 7.3.3 Environmental Nanosafety Assessment | 193 | ||
| 7.4 Conclusions | 195 | ||
| Acknowledgments | 195 | ||
| References | 195 | ||
| Chapter 8 Organ-on-chip Systems: An Emerging Platform for Toxicity Screening of Chemicals, Pharmaceuticals, and Nanomaterials | 203 | ||
| 8.1 Introduction | 203 | ||
| 8.2 Fabrication of Organ-on-chip Systems | 205 | ||
| 8.3 Examples of Organ-on-chip Systems | 207 | ||
| 8.3.1 Lung-on-chip Systems | 207 | ||
| 8.3.2 Liver-on-chip Systems | 209 | ||
| 8.3.3 Kidney-on-chip Systems | 210 | ||
| 8.3.4 Brain-on-chip Systems | 211 | ||
| 8.3.5 Heart-on-chip Systems | 213 | ||
| 8.3.6 Gut-on-chip Systems | 214 | ||
| 8.3.7 Skin-on-chip Systems | 217 | ||
| 8.3.8 Multiorgan-on-chip Systems | 218 | ||
| 8.4 Conclusions | 219 | ||
| Acknowledgments | 220 | ||
| References | 220 | ||
| Chapter 9 Progress Towards Risk Assessment for Engineered Nanomaterials | 232 | ||
| 9.1 Introduction | 232 | ||
| 9.2 Current Status in Risk Assessment of ENMs | 233 | ||
| 9.2.1 Swiss Precautionary Matrix | 234 | ||
| 9.2.2 NanoRisk Framework | 234 | ||
| 9.2.3 Comprehensive Environmental Assessment | 234 | ||
| 9.2.4 Cenarios® | 236 | ||
| 9.2.5 Control Banding/Expert Judgement | 236 | ||
| 9.2.6 Stoffenmanager Nano 1.0 | 237 | ||
| 9.2.7 Work Health and Safety Assessment Tool for Handling Engineered Nanomaterials | 237 | ||
| 9.2.8 NanoSafer | 238 | ||
| 9.2.9 Concern-driven Testing | 238 | ||
| 9.3 Risk Assessment Decision Support Tools | 238 | ||
| 9.3.1 Weight of Evidence | 238 | ||
| 9.3.2 Multi-criteria Decision Analysis | 238 | ||
| 9.4 Adverse Outcome Pathways | 239 | ||
| 9.5 Towards the Specification of Test Design for ENMs | 239 | ||
| 9.5.1 Improvement of Test Guidelines | 239 | ||
| 9.5.2 Quality Criteria for Studies Involving ENMs | 240 | ||
| 9.5.3 Structured Approaches for Test Design | 241 | ||
| 9.6 Conclusions | 243 | ||
| Acknowledgments | 244 | ||
| References | 244 | ||
| Chapter 10 Three-dimensional Models for In vitro Nanotoxicity Testing | 248 | ||
| 10.1 Introduction | 248 | ||
| 10.2 Limitations of Two-dimensional In vitro and In vivo Studies | 250 | ||
| 10.3 3D Models for Nanotoxicology | 253 | ||
| 10.3.1 Co-culture Models | 264 | ||
| 10.3.2 Spheroid Microtissues | 264 | ||
| 10.3.3 Complex Multicellular 3D Structures | 266 | ||
| 10.4 Conclusions | 269 | ||
| References | 270 | ||
| Chapter 11 Computational Modelling of Biological Responses to Engineered Nanomaterials | 276 | ||
| 11.1 Introduction | 276 | ||
| 11.2 Description and Characterization of ENMs | 279 | ||
| 11.3 Predictive Modelling | 281 | ||
| 11.3.1 NanoQSAR Models | 282 | ||
| 11.3.2 Grouping and Read-across | 285 | ||
| 11.4 Mechanistic Modelling | 286 | ||
| 11.5 Risk Assessment and the AOP Approach | 288 | ||
| 11.6 Standardization, Harmonization and the eNanoMapper Framework | 291 | ||
| 11.7 Discussion and Conclusions | 294 | ||
| Acknowledgments | 295 | ||
| References | 295 | ||
| Chapter 12 Computational Approaches for Predicting Nanotoxicity at the Molecular Level | 304 | ||
| 12.1 Introduction to Nanoscience and Nanotechnology | 304 | ||
| 12.2 Routes of Exposure to Nanomaterials in the Human Body | 305 | ||
| 12.3 Toxicity of Nanomaterials | 306 | ||
| 12.3.1 NM-Induced Perturbation in Biomolecules and their Outcomes | 307 | ||
| 12.3.2 Effect of Physicochemical Properties of NMs on Adsorbed Proteins | 308 | ||
| 12.3.3 Limitations in Studying NM-induced Conformational Changes in Biomolecules | 308 | ||
| 12.3.4 Experimental Limitations in Studying Intrinsically Disordered Proteins | 309 | ||
| 12.4 Molecular Dynamics Simulations | 310 | ||
| 12.4.1 Energy Minimization | 310 | ||
| 12.4.2 Periodic Boundary Conditions in MD | 311 | ||
| 12.4.3 Ensemble in MD Simulations | 312 | ||
| 12.5 Application of MD Simulations in Studying NM-Protein Interactions | 312 | ||
| 12.5.1 Effect of Surface Curvature and Surface Chemistries of NMs on the Structure of Proteins | 312 | ||
| 12.5.2 Effect of Secondary Structural Features of Proteins on Conformational Changes | 315 | ||
| 12.5.3 Interaction of NMs with Active Sites and Protein-Protein Interfaces | 315 | ||
| 12.5.4 Understanding the Formation of a Protein Corona on NMs using Molecular Simulations | 316 | ||
| 12.6 Effect of NMs on Intrinsically Disordered Proteins | 317 | ||
| 12.7 Nanomaterial-induced Perturbation in Plasma Membranes | 318 | ||
| 12.8 Conclusions | 319 | ||
| Acknowledgments | 320 | ||
| References | 320 | ||
| Chapter 13 Safety Guidelines: Recommendations by Various Nations | 328 | ||
| 13.1 Nanomaterials as Potentially Hazardous Substances | 328 | ||
| 13.2 Legal Framework in the European Union | 329 | ||
| 13.2.1 General | 329 | ||
| 13.2.2 Classification and Labelling | 330 | ||
| 13.2.3 REACh | 331 | ||
| 13.2.4 Safety Data Sheets | 333 | ||
| 13.2.5 Occupational Safety and Health - EU Minimum Standards | 334 | ||
| 13.2.6 EU Precautionary Approach | 335 | ||
| 13.3 Regulations in Germany | 336 | ||
| 13.3.1 Law on Chemicals (German: Chemikaliengesetz, ‘‘ChemG\") | 336 | ||
| 13.3.2 Hazardous Substances Ordinance (German: Gefahrstoffverordnung, ‘‘GefStoffV\") | 336 | ||
| 13.4 Technical Rules for Hazardous Substances | 338 | ||
| 13.5 Handling of Nanomaterials in the Actual Work Situation: Risk Assessment | 340 | ||
| 13.5.1 Control Banding | 340 | ||
| 13.5.2 Decision Criteria to Derive Occupational Safety Measures for Nanomaterials (‘‘Nano to Go!\") | 341 | ||
| 13.5.3 Control Strategies for Dry, Dusty and Insoluble Nanoparticles | 343 | ||
| Acknowledgments | 346 | ||
| References | 346 | ||
| Subject Index | 349 |