Metal Toxicology (eBook)

Front Cover 1
Metal Toxicology 4
Copyright Page 5
Table of Contents 6
Contributors 18
Preface 22
PART I: GENERAL PRINCIPLES 26
Chapter 1. Metal Disposition: An Analysis of Underlying Mechanisms 28
I. INTRODUCTION 28
II. METAL ABSORPTION 30
III. TRANSPORT OF TNEM IN BLOOD 38
IV. MECHANISM OF CELLULAR TNEM UPTAKE IN TARGET ORGANS 40
V. CELLULAR TRAPPING OF TNEM AND THEIR RELEASE 43
VI. EXCRETION OF TNEM 47
VII. APPROACH TO STEADY STATE: TOXICOLOGICAL IMPLICATIONS 48
VIII. CONCLUSIONS 49
REFERENCES 49
Chapter 2. Factors Influencing Metal Toxicity 56
I. INTRODUCTION 56
II. ESSENTIAL METALS 57
III. METAL-BINDING PROTEINS 61
IV. ETHANOL 62
V. AGE AND DEVELOPMENT 63
VI. GENETICS 66
REFERENCES 66
Chapter 3. Metal Carcinogenesis 72
I. INTRODUCTION 72
II. CHARACTERISTICS OF METALS AS TOXINS OR CARCINOGENS 73
III. PROBLEMS IN ASSESSING CARCINOGENIC RISK FROM METALS 74
IV. METALS AS HUMAN CARCINOGENS 76
V. METALS AS CARCINOGENS IN ANIMALS 79
VI. TARGET SITES OF THE CARCINOGENIC METALS 79
VII. TARGET SITE SPECIFICITY IN METAL CARCINOGENESIS 84
VIII. DUALITIES IN METAL CARCINOGENESIS 85
IX. HYPOTHETICAL MECHANISMS IN METAL CARCINOGENESIS 86
X. METAL-METAL INTERACTIONS IN METAL CARCINOGENESIS 88
XI. SUMMARY 89
REFERENCES 89
Chapter 4. Organ-Specific Therapeutic Intervention 96
I. INTRODUCTION 96
II. BLOOD, MARROW, BONE 99
III. IMMUNOTOXICITY 105
IV. LIVER TOXICITY 106
V. KIDNEY 110
VI. NEUROTOXICITY 113
VII. CARDIOVASCULAR 119
VIII. RESPIRATORY 119
IX. SKIN TOXICITY 120
X. REPRODUCTIVE TOXICITY 121
REFERENCES 124
Chapter 5. Molecular Techniques in Metal Toxicology 136
I. INTRODUCTION 136
II. MEASURING GENETIC CHANGES IN RESPONSE TO METALS 139
III. INTERVENTION IN CONTROL OF GENE EXPRESSION IN EUKARYOTES 152
IV. CELLULAR RESPONSE TO INTERVENTION IN GENE EXPRESSION 156
V. SUMMARY 158
ACKNOWLEDGMENT 158
REFERENCES 158
Chapter 6. Risk Assessment 166
I. INTRODUCTION 166
II. HAZARD IDENTIFICATION 167
III. DOSE-RESPONSE ASSESSMENT 172
IV. EXPOSURE ASSESSMENT 181
V. RISK CHARACTERIZATION 191
VI. USE OF RISK ASSESSMENT FOR METALS IN THE REGULATORY PROCESS 200
VII. CONCLUSIONS 205
REFERENCES 206
Chapter 7. Toxic Metals in Emerging Technologies 212
I. INTRODUCTION 212
II. CHEMICAL DISPOSITION STUDIES 213
III. BIOLOGICAL EFFECTS 214
IV. FUTURE RESEARCH DIRECTIONS 217
ACKNOWLEDGEMENTS 218
REFERENCES 218
PART II: TARGET ORGANS 222
Chapter 8. Nervous System 224
I. INTRODUCTION 224
II. INORGANIC AND ORGANIC MERCURY 225
III. INORGANIC AND ORGANIC LEAD 232
IV. ALUMINUM 239
V. TIN 242
VI. TELLURIUM 244
VII. ARSENIC 245
VIII. MANGANESE 246
REFERENCES 248
Chapter 9. Respiratory System 262
I. INTRODUCTION 262
II. ADVERSE LUNG EFFECTS OF INHALED METALS 268
III. MODULATING FACTORS OF METAL TOXICITY 283
REFERENCES 285
Chapter 10. The Effects of Arsenic, Lead, and Cadmium on the Cardiovascular System1 290
I. INTRODUCTION 290
II. ARSENIC 291
III. LEAD 294
IV. CADMIUM 299
ACKNOWLEDGMENT 304
REFERENCES 304
Chapter 11. Hematopoietic System 312
I. INTRODUCTION 312
II. HEMATOPOIETIC EFFECTS OF INDIVIDUAL METALS 313
ACKNOWLEDGMENT 325
REFERENCES 325
Chapter 12. Immune Modulation by Toxic Metals 330
I. INTRODUCTION 330
II. LEAD EFFECTS ON THE IMMUNE SYSTEM 332
III. CADMIUM EFFECTS ON IMMUNITY 345
IV. MERCURY EFFECTS ON THE IMMUNE SYSTEM 347
V. SUMMARY 353
ACKNOWLEDGMENT 354
REFERENCES 354
Chapter 13. Hepatotoxicity of Metals1 364
I. INTRODUCTION 364
II. CADMIUM 365
III. ARSENIC 371
IV. CONCLUSION 377
REFERENCES 378
Chapter 14. Metals Lesions of the Gastrointestinal Tract 388
I. INTRODUCTION 388
II. INFLAMMATORY LESIONS OF THE ESOPHAGUS AND STOMACH 389
III. SQUAMOUS CARCINOMA OF THE ESOPHAGUS 394
IV. SMALL INTESTINE 397
V. ADENOCARCINOMA OF THE SMALL AND LARGE INTESTINE 405
REFERENCES 408
Chapter 15. Renal Effects of Metals 414
I. INTRODUCTION 414
II. SUSCEPTIBILITY TO RENAL TOXICITY 415
III. MECHANISMS AND PATHOLOGY 417
IV. BIOMARKERS OF RENAL INJURY BY METALS 418
V. NEPHROTOXICITY OF SPECIFIC METALS 420
VI. SUMMARY 432
REFERENCES 432
Chapter 16. Gonadal-Specific Metal Toxicology 438
I. GENERAL INTRODUCTION 438
II. TESTES: TARGET ORGAN FOR CHEMICAL INJURY 440
III. CONCLUDING REMARKS 458
II. OVARY 459
ACKNOWLEDGMENT 462
REFERENCES 462
Chapter 17. Skin 472
I. INTRODUCTION 472
II. CONTACT DERMATITIS 476
III. RISK ASSESSMENT 485
REFERENCES 486
Chapter 18. Metal-Induced Osteotoxicities 490
I. INTRODUCTION 490
II. CADMIUM 494
III. LEAD 507
IV. ALUMINUM 517
ACKNOWLEDGMENTS 522
REFERENCES 523
Index 536