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 RiskBased 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 LongTerm PM Exposures 321 9.10 Other Morbidity Responses Affected by PM2.5 Components 323 9.11 Controlled ShortTerm 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 HealthRelated 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 FiberRelated Diseases/Processes 403 11.6 Biological Effects of SizeClassified Fibers in Laboratory Animals and Humans 405 11.7 Critical Fiber Parameters Affecting Disease Pathogenesis 407 11.8 Exposure-Response Relationships for AsbestosRelated Lung Disease: Human Experience 416 11.9 Exposure-Response Relationships for SVFRelated Disease: Human Experience 421 11.

10 Summary of Human Responses to LongTerm 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 EndocrineDisrupting 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 SingleExposure 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.