PREFACE ........................................................ xv
CONTRIBUTORS ................................................. 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 ........................................ 12
1.6. Ingestion Exposures and Gastrointestinal
Tract Effects ........................................ 18
1.7. Skin Exposure and Dermal Effects ..................... 19
1.8. Absorption through Membranes and
Systemic Circulation ................................. 20
1.9. Accumulation in Target Tissues and
Dosimetric Models .................................... 21
1.10. Indirect Measures of Past Exposures .................. 22
1.11. Characterization of Health ........................... 23
1.12. Exposure-Response Relationships ...................... 25
1.13. Study Options for Health Effects Studies ............. 31
References ................................................. 35
2. Perspectives on Individual and Community Risks ............. 39
2.1. Nature of Risk ....................................... 39
2.2. Identification and Quantification of Risks ........... 41
2.3. Risk Communication ................................... 46
2.4. Risk Reduction ....................................... 49
References ................................................. 52
3. Reducing Risks—An Environmental Engineering Perspective .... 55
3.1. Introduction ......................................... 55
3.2. Environmental Risk-Based Decision Making ............. 56
3.3. Applications and Use ................................. 60
3.4. Recent Information ................................... 67
3.5. Integrated Assessments ............................... 71
3.6. Summary 72. References ............................... 73
4. Clinical Perspective on Respiratory Toxicology .............. 77
4.1. Concepts of Exposure ................................. 78
4.2. Tools for Studying Individuals ....................... 79
4.3. Tools for Studying Populations ....................... 88
4.4. Cardiovascular Responses ............................. 95
4.5. Limitations of Clinical and Epidemiological
Assessments of the Effects of Inhaled Agents ......... 96
4.6. Advice and Counseling of Patients .................... 97
4.7. Summary .............................................. 99
References ................................................ 100
5. Industrial Perspectives: Translating the Knowledge Base
into Corporate Policies Programs and Practices for
Health Protection ......................................... 107
5.1. The Life Cycle of a Chemical: Many Points for
Possible Intervention ............................... 108
5.2. The Knowledge Base for the Identification of
Hazard Control Strategies ........................... 109
5.3. Industrial Hygiene and Occupational Health
Programs: Implementing the Knowledge Base ........... 111
5.4. Product Stewardship ................................. 114
5.5. Responsible Care® ................................... 117
5.6. Concluding Perspective .............................. 119
6. Drinking Water Disinfection By-Products ................... 121
6.1. Introduction ........................................ 121
6.2. Chemical Methods of Disinfection .................... 122
6.3. Chemical Nature and Occurrence of Disinfectant
By-Products ......................................... 124
6.4. Associations of Human Disease with Drinking
Water Disinfection .................................. 132
6.5. General Toxicological Properties of Disinfectants ... 144
6.6. General Toxicological Properties of Disinfectant
By-Products ......................................... 145
6.7. Carcinogenic Properties of Disinfectants ............ 154
6.8. Carcinogenic By-Products of Disinfectants ........... 154
6.9. Effects of Disinfectants and Their By-Products
on Reproduction ..................................... 165
6.10. Effects on Development .............................. 168
6.11. By-Products of Potential Interest ................... 170
6.12. Summary and Conclusions ............................. 172
Glossary .................................................. 174
References ................................................ 176
7. Food ...................................................... 197
7.1. Introduction ......................................... 197
7.2. Legal and Regulatory Framework in
the United States .................................... 201
7.3. Toxicity Test Requirements and Safety Criteria ....... 203
7.4. Substances Intentionally Added to Food ............... 208
7.5. Food Contaminants of Industrial Origin ............... 216
7.6. Constituents and Contaminants of Natural Origin ...... 219
7.7. Food Safety in the European Union .................... 229
7.8. Summary and Conclusion ............................... 234
Acronyms .................................................. 235
References ................................................ 235
8. Volatile Organic Compounds and Sick Building Syndrome ..... 241
8.1. Introduction ......................................... 241
8.2. Prevalence of Exposures to Volatile
Organic Compounds .................................... 242
8.3. Health and Volatile Organic Compounds ................ 245
8.4. Prevalence of the Sick Building Syndrome ............. 247
8.5. Dose-Response Relationships for Health Effects
Caused by Low-Level VOC Exposure ..................... 249
8.6. Guidelines for Volatile Organic Compounds in
Nonindustrial Indoor Environments-Principles
for Establishment of Guidelines ...................... 251
References ................................................ 254
9. Formaldehyde and Other Aldehydes .......................... 257
9.1. Background ........................................... 257
9.2. Single-Exposure Health Effects ....................... 269
9.3. Effects of Multiple Exposures ........................ 281
References ................................................ 292
10. Ambient Air Particulate Matter ............................ 317
10.1. Sources and Pathways for Human Exposure ............. 318
10.2. Ambient Air PM Concentrations ....................... 323
10.3. Extent of Population Exposures to Ambient Air PM .... 326
10.4. Nature of the Evidence for Human Health Effects
of Ambient Air PM ................................... 328
10.5. Epidemiological Evidence for Human Health Effects
of Ambient Air PM ................................... 329
10.6. Discussion and Current Knowledge on the Health
Effects of PM ....................................... 354
10.7. Standards and Exposure Guidelines ................... 356
References ................................................ 359
11. Arsenic ................................................... 367
11.1. Introduction ........................................ 367
11.2. Physical and Chemical Properties of Environmental
as and Its Compounds ................................ 368
11.3. Environmental Exposures to the General Population:
Sources and Standards ............................... 371
11.4. Pathways and Kinetics for in vivo Uptake
Distribution and Elimination ........................ 374
11.5. As Essentiality ..................................... 375
11.6. Health Effects and Exposure-Response
Relationships ....................................... 376
11.7. Biomarkers of Exposure Susceptibility
and Effect .......................................... 380
11.8. Mitigating Effects and Controlling Exposures ........ 381
References ................................................ 383
12. Asbestos and Other Mineral and Vitreous Fibers ............ 395
12.1. Important Special Properties of Fibers .............. 395
12.2. Exposures to Fibers ................................. 399
12.3. Fiber Deposition in the Respiratory Tract ........... 402
12.4. Fiber Retention Translocation Disintegration
and Dissolution ..................................... 404
12.5. Properties of Fibers Relevant to Disease ............ 413
12.6. Fiber-Related Diseases/Processes .................... 413
12.7. Review of Biological Effects of Size-Classified
Fibers in Animals and Humans ........................ 415
12.8. Critical Fiber Parameters Affecting Disease
Pathogenesis ........................................ 420
12.9. Exposure-Response Relationships for Asbestos-
Related Lung Cancer and Mesothelioma: Human
Experience .......................................... 429
12.10.Risk Assessment Issues .............................. 438
12.11.Key Factors Affecting Fiber Dosimetry and
Toxicity: Recapitulation and Synthesis .............. 443
Acknowledgments ........................................... 446
Acronyms .................................................. 446
References ................................................ 446
13. Benzene ................................................... 459
13.1. Benzene Exposure .................................... 460
13.2. Uptake .............................................. 462
13.3. Metabolism and Disposition .......................... 462
13.4. Mechanisms of Toxicity .............................. 471
13.5. Risk Assessment ..................................... 482
References ................................................ 486
14. Carbon Monoxide ........................................... 499
14.1. Introduction ........................................ 499
14.2. CO Exposure and Dosimetry ........................... 500
14.3. Mechanisms of CO Toxicity ........................... 501
14.4. Populations at Risk of Health Effects Due
to CO Exposure ...................................... 502
14.5. Regulatory Background ............................... 503
14.6. Health Effects of CO ................................ 505
14.7. Summary and Conclusions ............................. 515
Acknowledgments ........................................... 517
References ................................................ 517
15. Chromium .................................................. 529
15.1. Introduction ........................................ 529
15.2. Essentiality ........................................ 529
15.3. Environmental Exposures ............................. 530
15.4. Toxicological Effects ............................... 535
15.5. Exposure Guidelines and Standards ................... 543
References ................................................ 544
16. Diesel Exhaust ............................................ 551
16.1. Historical Overview ................................. 551
16.2. Composition of Diesel Exhaust ....................... 553
16.3. Exposures to Diesel Exhaust ......................... 559
16.4. Health Effects ...................................... 561
16.5. Current Issues ...................................... 609
Acknowledgments ........................................... 613
References ................................................ 613
17. Dioxins and Dioxin-Like Chemicals ......................... 633
17.1. Introduction ........................................ 633
17.2. Sources ............................................. 634
17.3. Toxicological Effects and Mechanisms of Action ...... 640
17.4. Mechanisms of Action ................................ 643
References ................................................ 651
18. Endocrine Active Chemicals: Broadening the Scope .......... 661
18.1. Introduction 661
18.2. Biomarkers: Terminology from Various Disciplines .... 664
18.3. End Points and Clinical Signs Associated with
Endocrine Activity .................................. 666
18.4. Environmental Chemicals and End Points:
Case Examples ....................................... 675
18.5. Developmental Origins of Health and Disease ......... 681
18.6. Transgenerational Effects ........................... 684
18.7. Conclusion .......................................... 686
References ................................................ 687
19. Secondhand Smoke .......................................... 703
19.1. Exposure to Secondhand Smoke ........................ 705
19.2. Health Effects of Involuntary Smoking in Children ... 711
19.3. Health Effects of Involuntary Smoking in Adults ..... 722
19.4. SHS and Coronary Heart Disease ...................... 730
19.5. Respiratory Symptoms and Illnesses in Adults ........ 734
19.6. Summary ............................................. 740
References ................................................ 741
20. Lead and Compounds ........................................ 757
20.1. Introduction ........................................ 757
20.2. Physical/Chemical Properties and Behavior of Lead
and Its Compounds ................................... 758
20.3. Lead in the Environment and Human Exposure .......... 761
20.4. Lead Absorption ..................................... 766
20.5. Distribution ........................................ 771
20.6. Kinetics ............................................ 774
20.7. Biomarkers .......................................... 781
20.8. Health Effects ...................................... 785
20.9. Mechanisms Underlying Lead Toxicity ................. 792
20.10.Treatment of Lead Toxicity .......................... 796
References ................................................ 798
21. Mercury ................................................... 811
21.1. Introduction ........................................ 811
21.2. Chemistry ........................................... 811
21.3. Sources ............................................. 812
21.4. Environmental Exposures ............................. 813
21.5. Occupational Exposures .............................. 815
21.6. Kinetics and Metabolism ............................. 816
21.7. Health Effects ...................................... 818
21.8. Prevention .......................................... 820
References ................................................ 821
22. Nitrogen Oxides ........................................... 823
22.1. Introduction ........................................ 823
22.2. Sources ............................................. 823
22.3. Nitrogen Dioxide .................................... 824
22.4. Nitric Oxide ........................................ 845
22.5. Nitric/Nitrous Acid ................................. 848
22.6. Inorganic Nitrates .................................. 849
References ................................................ 851
23. Ozone ..................................................... 869
23.1. Introduction ........................................ 869
23.2. Background on Exposures and Health-Related
Effects ............................................. 873
23.3. Effects of Short-Term Exposures to Ozone
in Humans ........................................... 877
23.4. Factors Affecting the Variability of
Responsiveness in Humans ............................ 890
23.5. Studies of Populations Exposed to Ozone
in Ambient Air ...................................... 892
23.6. Effects Observed in Studies in Laboratory
Animals ............................................. 900
23.7. Determinants of Responsiveness to Ozone Exposures
in Animal Studies ................................... 901
23.8. Effects of Multiple Day and Ambient Episode
Exposures ........................................... 908
23.9. Chronic Effects of Ambient Ozone Exposures .......... 910
23.10.Ambient Air Quality Standards and Guidelines ........ 917
23.11.Summary and Conclusions ............................. 920
Acknowledgment ............................................ 922
References ................................................ 922
24. Pesticides ................................................ 937
24.1. Evolving Patterns of Pesticide Use .................. 938
24.2. Export of Hazardous Pesticides ...................... 939
24.3. Exposure to Pesticides .............................. 939
24.4. Epidemiology of Acute Pesticide Poisoning ........... 942
24.5. Toxicity of Pesticides .............................. 943
24.6. Pesticides and Endocrine/Reproductive Toxicity ...... 949
24.7. Pesticides and Childhood Cancer ..................... 950
24.8. Legislative Framework ............................... 950
24.9. Conclusion: Issues for the Future ................... 952
References ................................................ 953
25. Sulfur Oxides — SO2, H2SO4, NH4HSO4 and (NH4)2SO4 ......... 957
25.1. Sources and Exposures ............................... 957
25.2. Health Effects ...................................... 961
25.3. Ambient Air Quality Standard and Guidelines ......... 989
Acknowledgments ........................................... 991
References ................................................ 991
26. Microwaves and Electromagnetic Fields .................... 1001
26.1. Background ......................................... 1003
26.2. Philosophical Approaches ........................... 1004
26.3. Standards Development .............................. 1005
26.4. Current Developments ............................... 1010
26.5. Protective Measures ................................ 1012
26.6. Conclusions ........................................ 1014
26.7. Glossary ........................................... 1015
References ............................................... 1016
27. Sources Levels and Effects of Manmade Ionizing
Radiation and Radioactivity .............................. 1021
27.1. Source Documents ................................... 1021
27.2. Special Units ...................................... 1022
27.3. Sources of Manmade Radioactivity and Radiation ..... 1024
27.4. Nuclear Fuel Cycle ................................. 1025
27.5. Discussion of Radiation Doses from the Nuclear
Fuel Cycle ......................................... 1038
27.6. Nuclear Weapons Complex ............................ 1043
27.7. Local Tropospheric and Global Fallout .............. 1048
27.8. Medical Exposures .................................. 1050
27.9. Industrial Uses (Other than the Nuclear Fuel
Cycle) ............................................. 1054
27.10.Consumer Products .................................. 1055
27.11.Overview of Potential Health Impacts of Natural
and Manmade Sources of Radioactivity ............... 1057
References ............................................... 1066
28. Noise: Its Effects and Control ........................... 1071
28.1. Definitions of Sound and Noise ..................... 1071
28.2. Noise Exposure is Widespread and Annoying .......... 1072
28.3. Effects of Loud Sounds and Noise on Hearing ........ 1075
28.4. Noise as a Stressor ................................ 1076
28.5. Noise and Sleep Interference ....................... 1077
28.6. Noise and Mental Health ............................ 1077
28.7. Noise Affects Children's Cognitive Language
and Learning Skills ................................ 1078
28.8. Impacts of Low-Frequency Noise ..................... 1079
28.9. Civility Responsibility and Noise .................. 1079
28.10.Controlling Noise .................................. 1080
28.11.Education and Public Awareness ..................... 1084
28.12.Summary ............................................ 1084
References ............................................... 1085
29. Radon and Lung Cancer .................................... 1089
29.1. Radon and Lung Cancer .............................. 1089
29.2. Outdoor Radon ...................................... 1093
29.3. Indoor Radon ....................................... 1097
29.4. The Other Radon 220Rn, Thoron ...................... 1100
29.5. Radon Epidemiology in Underground Mines ............ 1100
29.6. Residential Epidemiology ........................... 1102
29.7. Lung Dosimetry ..................................... 1104
29.8. Lung Cancer Models for Humans ...................... 1107
29.9. Childhood Exposure ................................. 1113
29.10.Animal Studies ..................................... 1114
29.11.Smoking and Radon .................................. 1114
29.12.Summary ............................................ 1115
References ............................................... 1116
30. Ultraviolet Radiation .................................... 1121
30.1. Introduction ....................................... 1121
30.2. Pathways for Human Exposure ........................ 1122
30.3. Sources of Ultraviolet Radiation ................... 1124
30.4. Biological Mechanisms Leading to Health Effects .... 1135
30.5. Ocular Effects ..................................... 1135
30.6. Nonmalignant Skin Effects .......................... 1138
30.7. Skin Cancer ........................................ 1140
30.8. Malignant Melanoma ................................. 1142
30.9. Immune System Effects .............................. 1146
30.10.Populations at Special Risk: Ocular Damage ......... 1147
30.11.Populations at Special Risks: Skin Effects ......... 1148
30.12.Applicable Standards and Exposure Guidelines ....... 1150
30.13.Techniques for Evaluating Actual or
Potential Exposures ............................... 1152
30.14. Summary ........................................... 1156
References ............................................... 1157
INDEX ........................................................ 1163
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