Environmental Toxicants

MORTON LIPPMANN, PHD, earned a Bachelor of Chemical Engineering at Cooper Union, an MS in Industrial Hygiene at Harvard School of Public Health, and a PhD in Environmental Health Science at New York University (NYU) School of Engineering. He is currently a professor of Environmental Medicine at NYU School of Medicine. He has spent his adult life researching the health effects of particulate matter (PM) in ambient air on public health. He has published over 370 research papers and two reference texts on environmental health science. GEORGE D. LEIKAUF earned his A.B at the University of California, Berkeley, his Ph.D. in environmental health science at New York University, and finished his postdoctoral training at CVRI-University of California, San Francisco. Throughout his career, he has developed several in vitro approaches to the study of pulmonary epithelial, cellular, and molecular responses to toxicants. Currently, he is a professor of Environmental and Occupational Health at the University of Pittsburgh, Graduate School of Public Health.

• Contributors xiiiPreface xvii1 Introduction and Background 11.1 Characterization of Chemical Contaminants 21.2 Human Exposures and Dosimetry 71.3 Chemical Exposures and Dose to Target Tissues 81.4 Concentration of Toxic Chemicals in Human Microenvironments 91.5 Inhalation Exposures and Respiratory Tract Effects 131.6 Ingestion Exposures and Gastrointestinal Tract Effects 191.7 Skin Exposure and Dermal Effects 201.8 Absorption Through Membranes and Systemic Circulation 211.9 Accumulation in Target Tissues and Dosimetric Models 221.10 Indirect Measures of Past Exposures 231.11 Characterization of Health 241.12 Exposure–Response Relationships 261.13 Study Options for Health Effects Studies 32References 372 Perspectives on Individual and Community Risk 412.1 Nature of Risk 422.2 Identification and Quantification of Risks 462.3 Risk Communication 512.4 Risk Reduction 54References 583 Reducing Risks: An Environmental Engineering Perspective 653.1 Introduction 653.2 Environmental Risk‐Based Decision Making 663.3 Applications and Use 703.4 Historic Background 783.5 Integrated Assessments 823.6 Summary 83References 834 Clinical Perspective on Respiratory Toxicology 874.1 Concepts of Exposure 884.2 Tools for Studying Individuals 904.3 Tools for Studying Populations 1014.4 Cardiovascular Responses 1084.5 Limitations of Clinical and Epidemiological Assessments of the Effects of Inhaled Agents 1104.6 Climate Change and Health 1114.7 Novel Exposures 1114.8 Advice and Counseling of Patients 1124.9 Summary 115References 1165 Industrial Perspectives: Translating the Knowledge Base into Corporate Policies, Programs, and Practices for Health Protection 1275.1 Introduction 1275.2 The Life Cycle of a Chemical: Many Points for Possible Intervention 1285.3 The Knowledge Base for the Identification of Hazard and Health Protection Control Strategies 1295.4 Industrial Hygiene and Occupational Health Programs : Implementing the Knowledge Base 1315.5 Product Stewardship 1385.6 Responsible Care 1425.7 Concluding Perspective 145Acknowledgment 145References 1456 Food Constituents and Contaminants 1496.1 Introduction 1496.2 Legal and Regulatory Framework in the United States 1526.3 Safety Criteria and Their Scientific Bases 1556.4 Nutrients 1636.5 Substances Intentionally Introduced into Food 1646.6 Food Contaminants of Industrial Origin 1716.7 Constituents and Contaminants of Natural Origin 1796.8 Compounds Produced During Food Storage and Preparation 1896.9 Dietary Supplements 1916.10 Food Safety Institutions Around the World 1926.11 Summary and Conclusion 193Acronyms 194References 1957 Acrolein and Unsaturated Aldehydes 2057.1 Background 2057.2 Cellular Exposure and Metabolism 2127.3 Single Exposure Health Effects 2307.4 Repeated Exposure Health Effects 2357.5 Conclusion 239References 2408 Chemical Weapons 2618.1 Overview 2618.2 Nerve Agents 2628.3 Respiratory Toxicants 2658.4 Vesicants 2668.5 Rodenticides 2718.6 Arsenicals 2738.7 Metabolic Poisons 2748.8 Summary 275Acknowledgments 275References 2759 Ambient Air Particulate Matter 2859.1 Introduction 2859.2 Background 2869.3 Sources and Pathways for Human Exposure 2909.4 Ambient Air PM Concentrations 2919.5 Population Exposures to Ambient Air PM 2929.6 Evidence for Adverse Human Health Effects Due to the Inhalation of Ambient Air PM 2939.7 Health Effects of Specific PM Components 3019.8 Chronic Exposures to PM2.5 and Components on Annual Mortality 3129.9 Pediatric Responses to Long‐Term PM Exposures 3219.10 Other Morbidity Responses Affected by PM2.5 Components 3239.11 Controlled Short‐Term Human Inhalation Exposure Studies 3259.12 Animal Inhalation Studies with Concentrated PM (Caps) 3269.13 Effects of PM Source Mixture Inhalation Exposures in Laboratory Animals 3329.14 NPACT Subchronic Caps Mouse Inhalation Studies 3359.15 Consistency, Coherence, and Implications to Public Health 3379.16 Most Influential PM2.5 Components as Causal Factors 3389.17 Daily Morbidity Effects and Coherence with Excess Daily Mortality 3399.18 Effects of PM2.5 Components in Toxicological Studies 3429.19 The Roles of PM2.5 Components on Health‐Related Responses 3439.20 Coherence of NPACT Toxicological and Epidemiological Responses 3449.21 Coherence of NPACT Study of CVD Effects in People and in Mice 3449.22 Coherence: Annual Human Annual Mortality with Aortic Plaque Progression in Apoe−/− Mice 3459.23 Traffic and So4 = in the NPACT Studies 3459.24 Holistic Perspectives on the Role of PM2.5 in CVD Effects 3469.25 Setting of NAAQS and/or Control Strategies for Ambient Air PM 3489.26 Research Needs 3519.27 Need for a More Comprehensive Air Quality Monitoring Program 3519.28 Conclusions 352References 35310 Arsenic 36710.1 Introduction 36710.2 Kinetics of as Uptake, Distribution, and Elimination 37310.3 Toxicity and Mechanisms of Toxicity 37510.4 Evidence of Human Diseases Caused by Arsenic 37710.5 Conclusions 380References 38011 Asbestos and Other Mineral and Vitreous Fibers 38911.1 Introduction 38911.2 Inhalation Exposures to Fibers 39311.3 Fiber Deposition in the Respiratory Tract 39511.4 Fiber Retention, Translocation, Disintegration, and Dissolution 39711.5 Fiber‐Related Diseases/Processes 40311.6 Biological Effects of Size‐Classified Fibers in Laboratory Animals and Humans 40511.7 Critical Fiber Parameters Affecting Disease Pathogenesis 40711.8 Exposure–Response Relationships for Asbestos‐Related Lung Disease: Human Experience 41611.9 Exposure–Response Relationships for SVF‐Related Disease: Human Experience 42111.10 Summary of Human Responses to Long‐Term Fiber Inhalation Exposures 42411.11 Summary of Pulmonary and Pleural Responses in Animals 42611.12 Overall Summary of In Vivo Biological Responses to Various Durable Fibers 43011.13 Risk Assessment Issues 43011.14 Risk Assessment Issues—SVFs 43411.15 Recapitulation and Synthesis: Factors Affecting Fiber Dosimetry and Toxicity 43611.16 Discussion 43811.17 Conclusions 439Acknowledgments 440Acronyms 440References 44112 Carbon Monoxide 45512.1 Introduction 45512.2 CO Exposure and Dosimetry 45612.3 Mechanisms of CO Toxicity 45812.4 Populations at Risk of Health Effects Due to CO Exposure 45912.5 Potential Risks for Pregnant Women, Fetuses, and Newborn Children 46012.6 Historical Regulatory Background 46012.7 Health Effects of CO 46112.8 Exposure and Relationship to COHb Concentrations 46512.9 Neurotoxicological and Behavioral Effects 47012.10 Fetal Developmental and Perinatal Effects 47112.11 CO as a Risk Factor in Cardiovascular Disease Development 47212.12 Summary and Conclusions 472References 47413 Chromium 48713.1 Introduction 48713.2 Exposure 48813.3 Chromium Uptake and Metabolism 49213.4 Toxicological Effects 49413.5 Mechanisms of Chromium Toxicity and Carcinogenicity 500References 50314 Diesel Exhaust and Lung Cancer Risk 51514.1 Historical Overview 51514.2 Composition of Diesel Engine Exhaust 51714.3 Environmental Exposures to Diesel Exhaust 52014.4 Cancer 52114.5 Conclusions 528Acknowledgments 529References 53015 Endocrine‐Disrupting Chemicals 53515.1 Introduction 53515.2 Modes of Action 53615.3 Selected Disease Endpoints 54215.4 Conclusion 547References 54816 Formaldehyde and Other Saturated Aldehydes 55516.1 Background 55516.2 Single‐Exposure Health Effects 57016.3 Effects of Multiple Exposures 580References 59717 Lead and Compounds 62717.1 Introduction 62717.2 Physical/Chemical Properties and Behavior of PB and its Compounds 62817.3 Lead in the Environment and Human Exposure 63117.4 Lead Absorption 63417.5 Distribution 63917.6 Kinetics 64217.7 Biomarkers 64817.8 Health Effects 65117.9 Mechanisms Underlying Lead Toxicity 65817.10 Treatment of Lead Toxicity 66117.11 Summation 663References 66318 Mercury 67718.1 Introduction 67718.2 Chemistry 67818.3 Sources 67818.4 Environmental Exposures 67918.5 Kinetics and Metabolism 68218.6 Absorption 68218.7 Distribution 68318.8 Elimination 68418.9 Health Effects 68518.10 Prevention 688References 68919 Cardiopulmonary Effects of Nanomaterials 69519.1 Introduction 69519.2 Nanoparticles: Scope and Toxicity 69619.3 Lessons Learned 69719.4 Particle Characterization 69819.5 Relevant Exposure Scenario 69819.6 NP Exposure 69919.7 Cardiovascular Effects Following Pulmonary NP Exposure 70019.8 Types of NP in Common Usage 70119.9 Case Study: Subchronic Effects of Inhaled Nickel Nanoparticles on the Progression of Atherosclerosis in a Hyperlipidemic Mouse Model 70919.10 Human Data 71019.11 Future Studies 71019.12 Summary 710References 71120 Nitrogen Oxides 72120.1 Introduction 72120.2 Sources of NOx 72320.3 Nitrogen Dioxide 72520.4 Nitric Oxide 75320.5 Nitric/Nitrous Acid 75620.6 Inorganic Nitrates 75720.7 Summary and Conclusions 759References 76121 Ozone 78321.1 Introduction 78321.2 Background on Exposures and Health‐Related Effects 78721.3 Effects of Short‐Term Exposures to Ozone in Humans 79021.4 Factors Affecting Responsiveness in Humans 80521.5 Mechanistic Studies in Laboratory Animals 80721.6 Studies of Populations Exposed to Ozone in Ambient Air 80821.7 Effects Observed in Studies in Laboratory Animals 81621.8 Effects of Other Pollutants on Responses to Ozone 82121.9 Effects of Multiday and Ambient Episode Exposures 82421.10 Cumulative Effects of Ambient Ozone Exposures 82621.11 Controlled Laboratory Exposure Studies: Animal Responses 82921.12 Standards and Exposure Guidelines 83321.13 Summary and Conclusions 835Acknowledgments 837References 83822 Pesticides 85522.1 Uses of Pesticides 85522.2 History of Pesticides 85622.3 Exposure to Pesticides 85722.4 Acute Poisoning with Pesticides 85822.5 Toxicity of Pesticides 85922.6 Pesticides as Endocrine Disruptors 86722.7 Pesticides and Developmental Neurotoxicity 86822.8 Legislative Framework 86822.9 Conclusion 870Acknowledgment 870References 87023 Radon and Lung Cancer 87723.1 Introduction 87723.2 History of Radon and Decay Product Measurement 88023.3 Indoor Measurements of 222RN 88123.4 Outdoor Measurements of 222RN 88223.5 Measurement of 222RN Decay Products 88423.6 Groundwater as a Source of Indoor 222RN 88523.7 220RN (Thoron) the Other Radon 88723.8 Radon Epidemiology in Underground Mines and Lung Cancer Risk 88823.9 Residential Radon Epidemiology Lung Cancer Models and Lung Cancer Risk 89023.10 Lung Dosimetry 89223.11 Regulations and Guidelines for 222RN Exposure 89723.12 Radon and Smoking 89823.13 Childhood 222RN Exposure 89923.14 Other Natural Background Exposure 90223.15 Summary 903Glossary 903References 90524 Secondhand Tobacco Smoke 91124.1 Introduction 91124.2 Exposure to Secondhand Smoke (SHS) 91224.3 Health Effects of Involuntary Smoking 91724.4 Control of Exposure to Secondhand Smoke 92124.5 Summary 922References 92325 Sulfur Oxides (SOx): SO2, H2SO4, NH4HSO4, and (NH4)2SO4 92725.1 Introduction 92725.2 Sources and Exposures 92825.3 Health Effects of So2 93225.4 Long‐Term Multi‐Pollutant Effects Studies 93925.5 Exposures to and Health Effects of Acidic Aerosols 94225.6 Ambient Air Quality Standard 96025.7 Who Guidelines 96025.8 Overall Discussion 96125.9 Conclusions 962Acknowledgment 962References 96226 World Trade Center (WTC) Dust 97326.1 Introduction 97326.2 Post‐Collapse Human Inhalation Exposures to WTC Dusts 97426.3 Potential Dosimetry of WTC Dusts 97826.4 Associations Between WTC Dust Inhalation and Health Effects 98026.5 Studies of Biologic Responses to WTC Dusts 98626.6 Possible Roles of Minor Mass Components as Causal Factors for Observed Health Effects 99126.7 Roles of Major Mass Components as Potential Causal Factors for Observed Health Effects 99226.8 Conclusions 993Acknowledgments 995References 995Index 999