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 xiii

Preface xvii

1 Introduction and Background 1

1.1 Characterization of Chemical Contaminants 2

1.2 Human Exposures and Dosimetry 7

1.3 Chemical Exposures and Dose to Target Tissues 8

1.4 Concentration of Toxic Chemicals in Human Microenvironments 9

1.5 Inhalation Exposures and Respiratory Tract Effects 13

1.6 Ingestion Exposures and Gastrointestinal Tract Effects 19

1.7 Skin Exposure and Dermal Effects 20

1.8 Absorption Through Membranes and Systemic Circulation 21

1.9 Accumulation in Target Tissues and Dosimetric Models 22

1.10 Indirect Measures of Past Exposures 23

1.11 Characterization of Health 24

1.12 Exposure–Response Relationships 26

1.13 Study Options for Health Effects Studies 32

References 37

2 Perspectives on Individual and Community Risk 41

2.1 Nature of Risk 42

2.2 Identification and Quantification of Risks 46

2.3 Risk Communication 51

2.4 Risk Reduction 54

References 58

3 Reducing Risks: An Environmental Engineering Perspective 65

3.1 Introduction 65

3.2 Environmental Risk‐Based Decision Making 66

3.3 Applications and Use 70

3.4 Historic Background 78

3.5 Integrated Assessments 82

3.6 Summary 83

References 83

4 Clinical Perspective on Respiratory Toxicology 87

4.1 Concepts of Exposure 88

4.2 Tools for Studying Individuals 90

4.3 Tools for Studying Populations 101

4.4 Cardiovascular Responses 108

4.5 Limitations of Clinical and Epidemiological Assessments of the Effects of Inhaled Agents 110

4.6 Climate Change and Health 111

4.7 Novel Exposures 111

4.8 Advice and Counseling of Patients 112

4.9 Summary 115

References 116

5 Industrial Perspectives: Translating the Knowledge Base into Corporate Policies, Programs, and Practices for Health Protection 127

5.1 Introduction 127

5.2 The Life Cycle of a Chemical: Many Points for Possible Intervention 128

5.3 The Knowledge Base for the Identification of Hazard and Health Protection Control Strategies 129

5.4 Industrial Hygiene and Occupational Health Programs : Implementing the Knowledge Base 131

5.5 Product Stewardship 138

5.6 Responsible Care 142

5.7 Concluding Perspective 145

Acknowledgment 145

References 145

6 Food Constituents and Contaminants 149

6.1 Introduction 149

6.2 Legal and Regulatory Framework in the United States 152

6.3 Safety Criteria and Their Scientific Bases 155

6.4 Nutrients 163

6.5 Substances Intentionally Introduced into Food 164

6.6 Food Contaminants of Industrial Origin 171

6.7 Constituents and Contaminants of Natural Origin 179

6.8 Compounds Produced During Food Storage and Preparation 189

6.9 Dietary Supplements 191

6.10 Food Safety Institutions Around the World 192

6.11 Summary and Conclusion 193

Acronyms 194

References 195

7 Acrolein and Unsaturated Aldehydes 205

7.1 Background 205

7.2 Cellular Exposure and Metabolism 212

7.3 Single Exposure Health Effects 230

7.4 Repeated Exposure Health Effects 235

7.5 Conclusion 239

References 240

8 Chemical Weapons 261

8.1 Overview 261

8.2 Nerve Agents 262

8.3 Respiratory Toxicants 265

8.4 Vesicants 266

8.5 Rodenticides 271

8.6 Arsenicals 273

8.7 Metabolic Poisons 274

8.8 Summary 275

Acknowledgments 275

References 275

9 Ambient Air Particulate Matter 285

9.1 Introduction 285

9.2 Background 286

9.3 Sources and Pathways for Human Exposure 290

9.4 Ambient Air PM Concentrations 291

9.5 Population Exposures to Ambient Air PM 292

9.6 Evidence for Adverse Human Health Effects Due to the Inhalation of Ambient Air PM 293

9.7 Health Effects of Specific PM Components 301

9.8 Chronic Exposures to PM2.5 and Components on Annual Mortality 312

9.9 Pediatric Responses to Long‐Term PM Exposures 321

9.10 Other Morbidity Responses Affected by PM2.5 Components 323

9.11 Controlled Short‐Term Human Inhalation Exposure Studies 325

9.12 Animal Inhalation Studies with Concentrated PM (Caps) 326

9.13 Effects of PM Source Mixture Inhalation Exposures in Laboratory Animals 332

9.14 NPACT Subchronic Caps Mouse Inhalation Studies 335

9.15 Consistency, Coherence, and Implications to Public Health 337

9.16 Most Influential PM2.5 Components as Causal Factors 338

9.17 Daily Morbidity Effects and Coherence with Excess Daily Mortality 339

9.18 Effects of PM2.5 Components in Toxicological Studies 342

9.19 The Roles of PM2.5 Components on Health‐Related Responses 343

9.20 Coherence of NPACT Toxicological and Epidemiological Responses 344

9.21 Coherence of NPACT Study of CVD Effects in People and in Mice 344

9.22 Coherence: Annual Human Annual Mortality with Aortic Plaque Progression in Apoe−/− Mice 345

9.23 Traffic and So4 = in the NPACT Studies 345

9.24 Holistic Perspectives on the Role of PM2.5 in CVD Effects 346

9.25 Setting of NAAQS and/or Control Strategies for Ambient Air PM 348

9.26 Research Needs 351

9.27 Need for a More Comprehensive Air Quality Monitoring Program 351

9.28 Conclusions 352

References 353

10 Arsenic 367

10.1 Introduction 367

10.2 Kinetics of as Uptake, Distribution, and Elimination 373

10.3 Toxicity and Mechanisms of Toxicity 375

10.4 Evidence of Human Diseases Caused by Arsenic 377

10.5 Conclusions 380

References 380

11 Asbestos and Other Mineral and Vitreous Fibers 389

11.1 Introduction 389

11.2 Inhalation Exposures to Fibers 393

11.3 Fiber Deposition in the Respiratory Tract 395

11.4 Fiber Retention, Translocation, Disintegration, and Dissolution 397

11.5 Fiber‐Related Diseases/Processes 403

11.6 Biological Effects of Size‐Classified Fibers in Laboratory Animals and Humans 405

11.7 Critical Fiber Parameters Affecting Disease Pathogenesis 407

11.8 Exposure–Response Relationships for Asbestos‐Related Lung Disease: Human Experience 416

11.9 Exposure–Response Relationships for SVF‐Related Disease: Human Experience 421

11.10 Summary of Human Responses to Long‐Term Fiber Inhalation Exposures 424

11.11 Summary of Pulmonary and Pleural Responses in Animals 426

11.12 Overall Summary of In Vivo Biological Responses to Various Durable Fibers 430

11.13 Risk Assessment Issues 430

11.14 Risk Assessment Issues—SVFs 434

11.15 Recapitulation and Synthesis: Factors Affecting Fiber Dosimetry and Toxicity 436

11.16 Discussion 438

11.17 Conclusions 439

Acknowledgments 440

Acronyms 440

References 441

12 Carbon Monoxide 455

12.1 Introduction 455

12.2 CO Exposure and Dosimetry 456

12.3 Mechanisms of CO Toxicity 458

12.4 Populations at Risk of Health Effects Due to CO Exposure 459

12.5 Potential Risks for Pregnant Women, Fetuses, and Newborn Children 460

12.6 Historical Regulatory Background 460

12.7 Health Effects of CO 461

12.8 Exposure and Relationship to COHb Concentrations 465

12.9 Neurotoxicological and Behavioral Effects 470

12.10 Fetal Developmental and Perinatal Effects 471

12.11 CO as a Risk Factor in Cardiovascular Disease Development 472

12.12 Summary and Conclusions 472

References 474

13 Chromium 487

13.1 Introduction 487

13.2 Exposure 488

13.3 Chromium Uptake and Metabolism 492

13.4 Toxicological Effects 494

13.5 Mechanisms of Chromium Toxicity and Carcinogenicity 500

References 503

14 Diesel Exhaust and Lung Cancer Risk 515

14.1 Historical Overview 515

14.2 Composition of Diesel Engine Exhaust 517

14.3 Environmental Exposures to Diesel Exhaust 520

14.4 Cancer 521

14.5 Conclusions 528

Acknowledgments 529

References 530

15 Endocrine‐Disrupting Chemicals 535

15.1 Introduction 535

15.2 Modes of Action 536

15.3 Selected Disease Endpoints 542

15.4 Conclusion 547

References 548

16 Formaldehyde and Other Saturated Aldehydes 555

16.1 Background 555

16.2 Single‐Exposure Health Effects 570

16.3 Effects of Multiple Exposures 580

References 597

17 Lead and Compounds 627

17.1 Introduction 627

17.2 Physical/Chemical Properties and Behavior of PB and its Compounds 628

17.3 Lead in the Environment and Human Exposure 631

17.4 Lead Absorption 634

17.5 Distribution 639

17.6 Kinetics 642

17.7 Biomarkers 648

17.8 Health Effects 651

17.9 Mechanisms Underlying Lead Toxicity 658

17.10 Treatment of Lead Toxicity 661

17.11 Summation 663

References 663

18 Mercury 677

18.1 Introduction 677

18.2 Chemistry 678

18.3 Sources 678

18.4 Environmental Exposures 679

18.5 Kinetics and Metabolism 682

18.6 Absorption 682

18.7 Distribution 683

18.8 Elimination 684

18.9 Health Effects 685

18.10 Prevention 688

References 689

19 Cardiopulmonary Effects of Nanomaterials 695

19.1 Introduction 695

19.2 Nanoparticles: Scope and Toxicity 696

19.3 Lessons Learned 697

19.4 Particle Characterization 698

19.5 Relevant Exposure Scenario 698

19.6 NP Exposure 699

19.7 Cardiovascular Effects Following Pulmonary NP Exposure 700

19.8 Types of NP in Common Usage 701

19.9 Case Study: Subchronic Effects of Inhaled Nickel Nanoparticles on the Progression of Atherosclerosis in a Hyperlipidemic Mouse Model 709

19.10 Human Data 710

19.11 Future Studies 710

19.12 Summary 710

References 711

20 Nitrogen Oxides 721

20.1 Introduction 721

20.2 Sources of NOx 723

20.3 Nitrogen Dioxide 725

20.4 Nitric Oxide 753

20.5 Nitric/Nitrous Acid 756

20.6 Inorganic Nitrates 757

20.7 Summary and Conclusions 759

References 761

21 Ozone 783

21.1 Introduction 783

21.2 Background on Exposures and Health‐Related Effects 787

21.3 Effects of Short‐Term Exposures to Ozone in Humans 790

21.4 Factors Affecting Responsiveness in Humans 805

21.5 Mechanistic Studies in Laboratory Animals 807

21.6 Studies of Populations Exposed to Ozone in Ambient Air 808

21.7 Effects Observed in Studies in Laboratory Animals 816

21.8 Effects of Other Pollutants on Responses to Ozone 821

21.9 Effects of Multiday and Ambient Episode Exposures 824

21.10 Cumulative Effects of Ambient Ozone Exposures 826

21.11 Controlled Laboratory Exposure Studies: Animal Responses 829

21.12 Standards and Exposure Guidelines 833

21.13 Summary and Conclusions 835

Acknowledgments 837

References 838

22 Pesticides 855

22.1 Uses of Pesticides 855

22.2 History of Pesticides 856

22.3 Exposure to Pesticides 857

22.4 Acute Poisoning with Pesticides 858

22.5 Toxicity of Pesticides 859

22.6 Pesticides as Endocrine Disruptors 867

22.7 Pesticides and Developmental Neurotoxicity 868

22.8 Legislative Framework 868

22.9 Conclusion 870

Acknowledgment 870

References 870

23 Radon and Lung Cancer 877

23.1 Introduction 877

23.2 History of Radon and Decay Product Measurement 880

23.3 Indoor Measurements of 222RN 881

23.4 Outdoor Measurements of 222RN 882

23.5 Measurement of 222RN Decay Products 884

23.6 Groundwater as a Source of Indoor 222RN 885

23.7 220RN (Thoron) the Other Radon 887

23.8 Radon Epidemiology in Underground Mines and Lung Cancer Risk 888

23.9 Residential Radon Epidemiology Lung Cancer Models and Lung Cancer Risk 890

23.10 Lung Dosimetry 892

23.11 Regulations and Guidelines for 222RN Exposure 897

23.12 Radon and Smoking 898

23.13 Childhood 222RN Exposure 899

23.14 Other Natural Background Exposure 902

23.15 Summary 903

Glossary 903

References 905

24 Secondhand Tobacco Smoke 911

24.1 Introduction 911

24.2 Exposure to Secondhand Smoke (SHS) 912

24.3 Health Effects of Involuntary Smoking 917

24.4 Control of Exposure to Secondhand Smoke 921

24.5 Summary 922

References 923

25 Sulfur Oxides (SOx): SO2, H2SO4, NH4HSO4, and (NH4)2SO4 927

25.1 Introduction 927

25.2 Sources and Exposures 928

25.3 Health Effects of So2 932

25.4 Long‐Term Multi‐Pollutant Effects Studies 939

25.5 Exposures to and Health Effects of Acidic Aerosols 942

25.6 Ambient Air Quality Standard 960

25.7 Who Guidelines 960

25.8 Overall Discussion 961

25.9 Conclusions 962

Acknowledgment 962

References 962

26 World Trade Center (WTC) Dust 973

26.1 Introduction 973

26.2 Post‐Collapse Human Inhalation Exposures to WTC Dusts 974

26.3 Potential Dosimetry of WTC Dusts 978

26.4 Associations Between WTC Dust Inhalation and Health Effects 980

26.5 Studies of Biologic Responses to WTC Dusts 986

26.6 Possible Roles of Minor Mass Components as Causal Factors for Observed Health Effects 991

26.7 Roles of Major Mass Components as Potential Causal Factors for Observed Health Effects 992

26.8 Conclusions 993

Acknowledgments 995

References 995

Index 999