Marc A. Williams, PhD, is an immunotoxicologist and Project Manager for Ecotoxicological Assessment, U.S. Army Public Health Center, Directorate of Toxicology, Aberdeen Proving Ground, Maryland. He is the author of more than 100 peer-reviewed articles, papers, book chapters, book titles, and scientific reports, with research interests in environmental toxicology, nanotoxicology, immunotoxicology and public health. Dr Williams is the Editor-in-Chief of Drug and Chemical Toxicology and a regular editor for Toxicology Letters.

• List of Contributors xvForeword xxiEditor Biography xxiiiSection I Introduction 11 A One Health Perspective and Introduction 3Marc A. Williams and Gunda Reddy1.1 Background 31.2 Structural and Logical Organization of the Book 9Acknowledgments 15References 15Section II Terrestrial and Aquatic Systems 192 Ecosafety of Nanomaterials in the Aquatic Environment 21Maria J. Bebianno, Thiago L. Rocha, José P. Pinheiro, Margarida Ribau Teixeira, and Fernanda Cassio2.1 Introduction 212.2 Inputs of NMs to the Aquatic Environment 232.3 HowWastewater Treatment Processes Act in the Removal of Nanomaterials? 232.4 So What Is Expected to Occur in WWTPs Processes? 242.5 The Importance of Understanding Speciation of NMs 272.6 Ecotoxicological Effects of NMs in Freshwater Organisms 302.7 Ecotoxicological Effects of NMs in Marine Organisms 342.8 Interactive Effects of NMs with Other Contaminants 382.9 Environmental Risk Assessment (ERA) of NMs 42Acknowledgments 43References 443 Changes in Toxicant Physicochemistry and Bioavailability During Sorption/Desorption Processes with TiO2 Nanoparticles in the Aqueous Phase 59Danae Patsiou, Martin R. S. McCoustra, Teresa F. Fernandes, and Theodore B. Henry3.1 Introduction 593.2 Properties of TiO2 NPs in the Aqueous Phase 613.2.1 Agglomeration 613.2.2 Oxidation of TiO2 NPs by UV Radiation 623.3 Sorption of Organic Substances to TiO2 NPs 643.3.1 Influence of Organic Matter on Sorption 643.3.2 Influence of TiO2 NP Surface Area on Sorption 643.3.3 Use of Bioavailability to Inform on Sorption of Organic Compounds on TiO2 NPs 663.4 Conclusions 72References 734 Behavior, Fate, and Toxicity of Engineered Nanoparticles in Estuarine and Coastal Environments 79Daniel M. Lyons and Petra Burić4.1 Introduction 794.2 Types of Nanoparticles: Sources/Products/Release Routes 804.3 Behavior of Nanoparticles in the Water Column 824.4 Biota, Trophic Transfer, Toxicity, and Mechanisms 844.5 Measurement Issues and Regulatory Environment 944.6 Modeling 944.7 Knowledge Gaps and Research Prospects 95References 965 Interactive Effects of Nanomaterials with Other Contaminants on Aquatic Organisms: nTiO2 as a Case Study 101Laura Canesi, Camilla Della Torre, Teresa Balbi, and Ilaria Corsi5.1 Introduction 1015.2 Interactive Effects of NPs with Other Contaminants in Aquatic Organisms: nTiO2 as a Case Study 1045.3 Interactions Between nTiO2 and Other Contaminants in Marine Invertebrates: The Example of the Bivalve Mytilus 1065.3.1 Effects of nTiO2 and Cd2+ 1065.3.2 Effects of nTiO2 and TCDD 1095.4 Interactions Between nTiO2 and Other Contaminants in Marine Fish: The Example of the European Sea Bass (Dicentrarchus labrax) 1115.5 Interactive Effects of NPs with Other Contaminants in Marine Species: Importance of Exposure Media 1145.6 Concluding Remarks 115Acknowledgments 115References 1156 Soil Nano-ecotoxicology: What Have We Learned from Standard Tests and What May We Be Missing? 121David J. Spurgeon, Elma Lahive, Carolin Schultz, and Claus Svendsen6.1 Introduction 1216.2 Development of Standard Test Methods and Their Application to Nanomaterials 1226.3 From Soil Ecotoxicological Tests to Risk Assessment 1276.4 Looking Beyond Standardized Tests Toward Effects in Ecosystems 1286.4.1 Choice of Test Species 1296.4.2 Short-Term and Long-Term Effects of Particle “Aging” on Toxicity in Natural Environments 1316.4.3 How Soil Properties Interact with Nanomaterial Properties to Determine Bioavailability 1336.4.4 Nanomaterial Bioaccumulation and Food Chain Transfer 1356.4.5 Short-Term Tests Predict Long-Term Effects 1366.5 Standard Ecotoxicological Tests: A Blessing and A Curse? 138Acknowledgments 139References 1407 Impacts of Magnetic Iron Oxide Nanoparticles in Terrestrial and Aquatic Environments 147Renato Grillo and Leonardo F. Fraceto7.1 Introduction 1477.1.1 Magnetic Nanoparticles and Their Properties 1477.1.2 Commercial Importance and Applications of IONPs 1497.1.3 Potential Toxic Effects of Magnetic Iron Oxide Nanoparticles 1517.2 Gaps and Obstacles 1557.3 Conclusions 158Acknowledgments 158References 1588 Carbon Nanotubes: Sublethal Effects and Unique Mechanisms of Toxicity in Aquatic Species 165Tara Sabo-Attwood, Christine Ngan, Candice Lavelle, Jaime Plazas-Tuttle, and Navid B. Saleh8.1 Carbon Nanotubes in Aquatic Environments 1658.2 Classical Toxicity: What We Have Learned 1678.3 Unique Mechanisms and Effects 1688.3.1 Nutrient Depletion 1688.3.2 Immune Modulation 1708.3.3 Influence on Co-contaminants 1728.4 Next-Generation Nanomaterials: Nanohybrids 1748.4.1 Variation in Nanohybrid Composition and Environmentally Relevant Properties 1748.4.2 Toxic Responses Demonstrated by NHs 1758.5 Future Perspectives 176Acknowledgments 176References 1769 Surface Reactivity of Anatase and Rutile Samples: Relationship with Toxicity on Aquatic Organisms 187Charlotte Hurel, Norbert Jordan, Ulrike Gerber, Stephan Weiss, Bernd Kubier, and Reinhard Kleeberg9.1 Introduction 1879.2 TiO2 Solid Phase Characterization 1909.3 Potentiometric Titrations 1949.4 Electrophoresis Measurements 1969.4.1 In NaNO3 1969.4.2 In Synthetic Freshwater (SFW) 1989.5 Size Measurements of the Agglomerates 1989.5.1 In NaNO3 1999.5.2 In Synthetic Freshwater (SFW) 1999.6 Ecotoxicity Tests 2019.6.1 Rotifer Toxicity Test 2019.6.2 Microcrustacean Toxicity Test 2039.6.3 Diatoms Toxicity Test 2049.7 Discussion 2069.8 Conclusions 208Acknowledgments 208References 20910 Cardiorespiratory Toxicity of Nanoparticles in Aquatic Environments 213Christopher A. Dieni and Tyson J. MacCormack10.1 Introduction 21310.2 Cellular and Molecular Mechanisms of Engineered Nanomaterial Toxicity 21410.2.1 Uptake-Independent Mechanisms 21510.2.1.1 Accumulation on Cell Surfaces and Interference with Membrane and Transport Functions 21610.2.1.2 Activation of Cell Surface Inflammatory Receptors 21610.2.1.3 Uptake-Independent Generation of Reactive Oxygen Species 21910.2.2 Uptake-Dependent Mechanisms 22110.2.2.1 Disruption of Ion Transporters by Intact Nanostructures and Ion Products and Physiological Regulation 22310.2.2.2 Activation of Systemic Immunity 22510.3 Complement 22510.4 Phagocytosis 22610.5 Conclusions and Ecological Perspectives 227References 228Section III Human Systems 23711 Air Pollution and Neurodevelopmental Disorders 239Joshua L. Allen, Carolyn Klocke, Keith Morris-Schaffer, Katherine Conrad, Marissa Sobolewski, and Deborah A. Cory-Slechta11.1 Air Pollution and the Brain 23911.1.1 The Brain as a Target of Air Pollution 24011.2 Air Pollution and Neurodevelopmental Disorders 24111.2.1 Shared Co-morbidities of Neurodevelopmental Disorders 24211.2.2 Potential Mechanisms of Air Pollution Associations with Neurodevelopmental Disorders 24311.2.2.1 Microglial Activation and Inflammation 24311.2.2.2 Ventriculomegaly, White Matter Damage, and Consequent Interhemispheric Dysconnectivity 24411.2.2.3 Altered Glutamate and Dopamine 24511.3 An Animal Model of UFP-Induced Developmental Neuropathology and Behavioral Disorders 24511.3.1 Developmental CAPS Exposures of Mice Produce Male-Specific Microglial Activation 24611.3.2 Developmental CAPS Exposures of Mice Produce Male-Specific Ventriculomegaly 24711.3.3 Developmental CAPS Exposures of Mice Produce Male-Specific White Matter Tract Disruption 24711.3.3.1 Corpus Callosum Size 24811.3.3.2 Corpus Callosum Myelination 25011.3.4 Developmental CAPS Exposures of Mice Elevate Glutamate Levels and Result in Male-Specific Excitatory–Inhibitory Imbalance 25011.3.5 Developmental CAPS Exposures of Mice Are Associated with Impulsive-Like Behavior 25111.4 Summary and Conclusions 253References 25612 Toxicity of Nanomaterials to the Gastrointestinal Tract 277Penelope A. Rice12.1 Introduction 27712.2 GI Physiology and Toxicity Testing 27912.3 Nanomaterial Toxicity Assessment: Challenges 28612.4 Toxicity of Specific Nanomaterial Types 28912.4.1 Titanium Dioxide 28912.4.2 Silica 30512.4.3 Nanosilver 31112.4.4 ZnO Nanoparticles 31912.4.5 Carbon Nanotubes and Fullerenes 32712.5 Miscellaneous Nanomaterials 33212.6 Analysis and Conclusions 337References 33813 The Mucosal Microbiome: Impact of Nanoparticles and Nanomaterials 353Katherine M. Williams, Kuppan Gokulan, and Sangeeta Khare13.1 Introduction 35313.2 Types of Nanoparticles and Human Exposure 35413.3 Factors Influencing Nanomaterial/Microbiota Interactions in the Intestinal Mucosal Environment 35613.3.1 Nanomaterial-Specific Factors 35613.3.2 Gut Environment-Specific Factors 35713.3.3 Protein Corona 35813.4 Nanomaterial Effects on Bacterial Microbiota 35813.4.1 Metallic NM 36113.4.1.1 Antibacterial Activity 36113.4.1.2 Impact in Gut Models 36213.4.2 Metal Oxide NM 36313.4.2.1 Antibacterial Activity 36313.4.2.2 Impact in Gut Models 36413.4.3 Carbon-Based NM 36413.4.3.1 Antibacterial Activity 36413.4.3.2 Impact in Gut Models 36613.5 Nanomaterial Effects on Viral and Fungal Microbiota 36613.6 Conclusions 36713.6.1 Antibacterial Activity of NMs 36713.6.2 Evidence for NM Effects on Gut Mucosal Microbiota 36713.6.3 Strategies for Assessing NM–Microbiota Effects 36813.6.4 Direction for Future Research 37013.6.5 Conclusion 372References 37214 Human Health Impacts and Immunotoxicology of Metal Nanoparticles and Nanomaterials – An Overview 383Gregory P. Nichols and Jason Davis14.1 Introduction and Background 38314.2 Welding Fumes as Surrogates for Metal Nanoparticles 38414.3 Immune-Related Health Effects 38514.4 Oxidative Stress and Immunologic Effects 38614.5 Conclusion 38714.6 Immune-Triggered Human Health Effects of Metal and Metal Oxide Nanoparticles 38714.7 Immune Interaction 38714.8 Cellular Mechanisms of Injury 38914.9 Oxidative Stress 38914.10 Interaction with Cellular Membranes and Proteins 39114.11 Disruption of Signaling Pathways 39114.12 Immune Response 39214.13 Immunosuppression 39214.14 Inflammation and Autoimmunity 39314.15 Sensitivity/Hypersensitivity 39414.16 Summary 396References 39615 Vasculotoxicity of Metal-Based Nanoparticles 401Maria S. Sepúlveda and Jiejun Gao15.1 Nanoparticles in the Environment 40115.2 Vascular Development 40215.3 Critical Issues in Assessing the Toxicity of NPs 40315.4 Vascular Toxicity of NPs In Vitro 40415.5 Vascular Toxicity of NPs In Vivo 40915.6 Movement of NPs Through the Blood Brain Barrier (BBB) 41215.7 Conclusions 413List of Abbreviations 413References 415Section IV Future Directions and Gaps in the Knowledge 42316 Knowledge Gaps, Future Directions, and the Emergence of Nanoplastics as an Environmental Threat Pollutant 425Marc A. Williams and Desmond I. Bannon16.1 Current Concerns and Scope of the Problem 42516.2 A survey of the Identified Knowledge Gaps and Needs for Future Research 42716.3 Knowledge Gaps – Aquatic and Terrestrial Ecotoxicology 42816.4 Knowledge Gaps – Adverse Health Effects in Humans 43516.5 Emerging Threats and Future Directions 43916.5.1 Nanoplastics – An Emergent Environmental Threat Pollutant 44016.6 Conclusions and Other Considerations 444References 446Index 453

Marc A. Williams, PhD, is an immunotoxicologist and Project Manager for Ecotoxicological Assessment, U.S. Army Public Health Center, Directorate of Toxicology, Aberdeen Proving Ground, Maryland. He is the author of more than 100 peer-reviewed articles, papers, book chapters, book titles, and scientific reports, with research interests in environmental toxicology, nanotoxicology, immunotoxicology and public health. Dr Williams is the Editor-in-Chief of Drug and Chemical Toxicology and a regular editor for Toxicology Letters.

• List of Contributors xvForeword xxiEditor Biography xxiiiSection I Introduction 11 A One Health Perspective and Introduction 3Marc A. Williams and Gunda Reddy1.1 Background 31.2 Structural and Logical Organization of the Book 9Acknowledgments 15References 15Section II Terrestrial and Aquatic Systems 192 Ecosafety of Nanomaterials in the Aquatic Environment 21Maria J. Bebianno, Thiago L. Rocha, José P. Pinheiro, Margarida Ribau Teixeira, and Fernanda Cassio2.1 Introduction 212.2 Inputs of NMs to the Aquatic Environment 232.3 HowWastewater Treatment Processes Act in the Removal of Nanomaterials? 232.4 So What Is Expected to Occur in WWTPs Processes? 242.5 The Importance of Understanding Speciation of NMs 272.6 Ecotoxicological Effects of NMs in Freshwater Organisms 302.7 Ecotoxicological Effects of NMs in Marine Organisms 342.8 Interactive Effects of NMs with Other Contaminants 382.9 Environmental Risk Assessment (ERA) of NMs 42Acknowledgments 43References 443 Changes in Toxicant Physicochemistry and Bioavailability During Sorption/Desorption Processes with TiO2 Nanoparticles in the Aqueous Phase 59Danae Patsiou, Martin R. S. McCoustra, Teresa F. Fernandes, and Theodore B. Henry3.1 Introduction 593.2 Properties of TiO2 NPs in the Aqueous Phase 613.2.1 Agglomeration 613.2.2 Oxidation of TiO2 NPs by UV Radiation 623.3 Sorption of Organic Substances to TiO2 NPs 643.3.1 Influence of Organic Matter on Sorption 643.3.2 Influence of TiO2 NP Surface Area on Sorption 643.3.3 Use of Bioavailability to Inform on Sorption of Organic Compounds on TiO2 NPs 663.4 Conclusions 72References 734 Behavior, Fate, and Toxicity of Engineered Nanoparticles in Estuarine and Coastal Environments 79Daniel M. Lyons and Petra Burić4.1 Introduction 794.2 Types of Nanoparticles: Sources/Products/Release Routes 804.3 Behavior of Nanoparticles in the Water Column 824.4 Biota, Trophic Transfer, Toxicity, and Mechanisms 844.5 Measurement Issues and Regulatory Environment 944.6 Modeling 944.7 Knowledge Gaps and Research Prospects 95References 965 Interactive Effects of Nanomaterials with Other Contaminants on Aquatic Organisms: nTiO2 as a Case Study 101Laura Canesi, Camilla Della Torre, Teresa Balbi, and Ilaria Corsi5.1 Introduction 1015.2 Interactive Effects of NPs with Other Contaminants in Aquatic Organisms: nTiO2 as a Case Study 1045.3 Interactions Between nTiO2 and Other Contaminants in Marine Invertebrates: The Example of the Bivalve Mytilus 1065.3.1 Effects of nTiO2 and Cd2+ 1065.3.2 Effects of nTiO2 and TCDD 1095.4 Interactions Between nTiO2 and Other Contaminants in Marine Fish: The Example of the European Sea Bass (Dicentrarchus labrax) 1115.5 Interactive Effects of NPs with Other Contaminants in Marine Species: Importance of Exposure Media 1145.6 Concluding Remarks 115Acknowledgments 115References 1156 Soil Nano-ecotoxicology: What Have We Learned from Standard Tests and What May We Be Missing? 121David J. Spurgeon, Elma Lahive, Carolin Schultz, and Claus Svendsen6.1 Introduction 1216.2 Development of Standard Test Methods and Their Application to Nanomaterials 1226.3 From Soil Ecotoxicological Tests to Risk Assessment 1276.4 Looking Beyond Standardized Tests Toward Effects in Ecosystems 1286.4.1 Choice of Test Species 1296.4.2 Short-Term and Long-Term Effects of Particle “Aging” on Toxicity in Natural Environments 1316.4.3 How Soil Properties Interact with Nanomaterial Properties to Determine Bioavailability 1336.4.4 Nanomaterial Bioaccumulation and Food Chain Transfer 1356.4.5 Short-Term Tests Predict Long-Term Effects 1366.5 Standard Ecotoxicological Tests: A Blessing and A Curse? 138Acknowledgments 139References 1407 Impacts of Magnetic Iron Oxide Nanoparticles in Terrestrial and Aquatic Environments 147Renato Grillo and Leonardo F. Fraceto7.1 Introduction 1477.1.1 Magnetic Nanoparticles and Their Properties 1477.1.2 Commercial Importance and Applications of IONPs 1497.1.3 Potential Toxic Effects of Magnetic Iron Oxide Nanoparticles 1517.2 Gaps and Obstacles 1557.3 Conclusions 158Acknowledgments 158References 1588 Carbon Nanotubes: Sublethal Effects and Unique Mechanisms of Toxicity in Aquatic Species 165Tara Sabo-Attwood, Christine Ngan, Candice Lavelle, Jaime Plazas-Tuttle, and Navid B. Saleh8.1 Carbon Nanotubes in Aquatic Environments 1658.2 Classical Toxicity: What We Have Learned 1678.3 Unique Mechanisms and Effects 1688.3.1 Nutrient Depletion 1688.3.2 Immune Modulation 1708.3.3 Influence on Co-contaminants 1728.4 Next-Generation Nanomaterials: Nanohybrids 1748.4.1 Variation in Nanohybrid Composition and Environmentally Relevant Properties 1748.4.2 Toxic Responses Demonstrated by NHs 1758.5 Future Perspectives 176Acknowledgments 176References 1769 Surface Reactivity of Anatase and Rutile Samples: Relationship with Toxicity on Aquatic Organisms 187Charlotte Hurel, Norbert Jordan, Ulrike Gerber, Stephan Weiss, Bernd Kubier, and Reinhard Kleeberg9.1 Introduction 1879.2 TiO2 Solid Phase Characterization 1909.3 Potentiometric Titrations 1949.4 Electrophoresis Measurements 1969.4.1 In NaNO3 1969.4.2 In Synthetic Freshwater (SFW) 1989.5 Size Measurements of the Agglomerates 1989.5.1 In NaNO3 1999.5.2 In Synthetic Freshwater (SFW) 1999.6 Ecotoxicity Tests 2019.6.1 Rotifer Toxicity Test 2019.6.2 Microcrustacean Toxicity Test 2039.6.3 Diatoms Toxicity Test 2049.7 Discussion 2069.8 Conclusions 208Acknowledgments 208References 20910 Cardiorespiratory Toxicity of Nanoparticles in Aquatic Environments 213Christopher A. Dieni and Tyson J. MacCormack10.1 Introduction 21310.2 Cellular and Molecular Mechanisms of Engineered Nanomaterial Toxicity 21410.2.1 Uptake-Independent Mechanisms 21510.2.1.1 Accumulation on Cell Surfaces and Interference with Membrane and Transport Functions 21610.2.1.2 Activation of Cell Surface Inflammatory Receptors 21610.2.1.3 Uptake-Independent Generation of Reactive Oxygen Species 21910.2.2 Uptake-Dependent Mechanisms 22110.2.2.1 Disruption of Ion Transporters by Intact Nanostructures and Ion Products and Physiological Regulation 22310.2.2.2 Activation of Systemic Immunity 22510.3 Complement 22510.4 Phagocytosis 22610.5 Conclusions and Ecological Perspectives 227References 228Section III Human Systems 23711 Air Pollution and Neurodevelopmental Disorders 239Joshua L. Allen, Carolyn Klocke, Keith Morris-Schaffer, Katherine Conrad, Marissa Sobolewski, and Deborah A. Cory-Slechta11.1 Air Pollution and the Brain 23911.1.1 The Brain as a Target of Air Pollution 24011.2 Air Pollution and Neurodevelopmental Disorders 24111.2.1 Shared Co-morbidities of Neurodevelopmental Disorders 24211.2.2 Potential Mechanisms of Air Pollution Associations with Neurodevelopmental Disorders 24311.2.2.1 Microglial Activation and Inflammation 24311.2.2.2 Ventriculomegaly, White Matter Damage, and Consequent Interhemispheric Dysconnectivity 24411.2.2.3 Altered Glutamate and Dopamine 24511.3 An Animal Model of UFP-Induced Developmental Neuropathology and Behavioral Disorders 24511.3.1 Developmental CAPS Exposures of Mice Produce Male-Specific Microglial Activation 24611.3.2 Developmental CAPS Exposures of Mice Produce Male-Specific Ventriculomegaly 24711.3.3 Developmental CAPS Exposures of Mice Produce Male-Specific White Matter Tract Disruption 24711.3.3.1 Corpus Callosum Size 24811.3.3.2 Corpus Callosum Myelination 25011.3.4 Developmental CAPS Exposures of Mice Elevate Glutamate Levels and Result in Male-Specific Excitatory–Inhibitory Imbalance 25011.3.5 Developmental CAPS Exposures of Mice Are Associated with Impulsive-Like Behavior 25111.4 Summary and Conclusions 253References 25612 Toxicity of Nanomaterials to the Gastrointestinal Tract 277Penelope A. Rice12.1 Introduction 27712.2 GI Physiology and Toxicity Testing 27912.3 Nanomaterial Toxicity Assessment: Challenges 28612.4 Toxicity of Specific Nanomaterial Types 28912.4.1 Titanium Dioxide 28912.4.2 Silica 30512.4.3 Nanosilver 31112.4.4 ZnO Nanoparticles 31912.4.5 Carbon Nanotubes and Fullerenes 32712.5 Miscellaneous Nanomaterials 33212.6 Analysis and Conclusions 337References 33813 The Mucosal Microbiome: Impact of Nanoparticles and Nanomaterials 353Katherine M. Williams, Kuppan Gokulan, and Sangeeta Khare13.1 Introduction 35313.2 Types of Nanoparticles and Human Exposure 35413.3 Factors Influencing Nanomaterial/Microbiota Interactions in the Intestinal Mucosal Environment 35613.3.1 Nanomaterial-Specific Factors 35613.3.2 Gut Environment-Specific Factors 35713.3.3 Protein Corona 35813.4 Nanomaterial Effects on Bacterial Microbiota 35813.4.1 Metallic NM 36113.4.1.1 Antibacterial Activity 36113.4.1.2 Impact in Gut Models 36213.4.2 Metal Oxide NM 36313.4.2.1 Antibacterial Activity 36313.4.2.2 Impact in Gut Models 36413.4.3 Carbon-Based NM 36413.4.3.1 Antibacterial Activity 36413.4.3.2 Impact in Gut Models 36613.5 Nanomaterial Effects on Viral and Fungal Microbiota 36613.6 Conclusions 36713.6.1 Antibacterial Activity of NMs 36713.6.2 Evidence for NM Effects on Gut Mucosal Microbiota 36713.6.3 Strategies for Assessing NM–Microbiota Effects 36813.6.4 Direction for Future Research 37013.6.5 Conclusion 372References 37214 Human Health Impacts and Immunotoxicology of Metal Nanoparticles and Nanomaterials – An Overview 383Gregory P. Nichols and Jason Davis14.1 Introduction and Background 38314.2 Welding Fumes as Surrogates for Metal Nanoparticles 38414.3 Immune-Related Health Effects 38514.4 Oxidative Stress and Immunologic Effects 38614.5 Conclusion 38714.6 Immune-Triggered Human Health Effects of Metal and Metal Oxide Nanoparticles 38714.7 Immune Interaction 38714.8 Cellular Mechanisms of Injury 38914.9 Oxidative Stress 38914.10 Interaction with Cellular Membranes and Proteins 39114.11 Disruption of Signaling Pathways 39114.12 Immune Response 39214.13 Immunosuppression 39214.14 Inflammation and Autoimmunity 39314.15 Sensitivity/Hypersensitivity 39414.16 Summary 396References 39615 Vasculotoxicity of Metal-Based Nanoparticles 401Maria S. Sepúlveda and Jiejun Gao15.1 Nanoparticles in the Environment 40115.2 Vascular Development 40215.3 Critical Issues in Assessing the Toxicity of NPs 40315.4 Vascular Toxicity of NPs In Vitro 40415.5 Vascular Toxicity of NPs In Vivo 40915.6 Movement of NPs Through the Blood Brain Barrier (BBB) 41215.7 Conclusions 413List of Abbreviations 413References 415Section IV Future Directions and Gaps in the Knowledge 42316 Knowledge Gaps, Future Directions, and the Emergence of Nanoplastics as an Environmental Threat Pollutant 425Marc A. Williams and Desmond I. Bannon16.1 Current Concerns and Scope of the Problem 42516.2 A survey of the Identified Knowledge Gaps and Needs for Future Research 42716.3 Knowledge Gaps – Aquatic and Terrestrial Ecotoxicology 42816.4 Knowledge Gaps – Adverse Health Effects in Humans 43516.5 Emerging Threats and Future Directions 43916.5.1 Nanoplastics – An Emergent Environmental Threat Pollutant 44016.6 Conclusions and Other Considerations 444References 446Index 453