Human toxicology of chemical mixtures : toxic consequences beyond the impact of one-component product and environmental exposures

In this important reference work, Zeliger catalogs the known effects of chemical mixtures on the human body and also proposes a framework for understanding and predicting their actions in terms of lipophile (fat soluble) / hydrophile (water soluble) interactions. The author’s focus is on illnesses that ensue following exposures to mixtures of chemicals that cannot be attributed to any one component of the mixture. In the first part the mechanisms of chemical absorption at a molecular and macromolecular level are explained, as well as the body’s methods of defending itself against xenobiotic intrusion. Part II examines the sources of the chemicals discusssed, looking at air and water pollution, food additives, pharmaceuticals, etc. Part III, which includes numerous case studies, examines specific effects of particular mixtures on particular body systems and organs and presents a theoretical framework for predicting what the effects of uncharacterized mixtures might be. Part IV covers regulatory requirements and the need to adjust recommended exposure levels for products containing mixtures. It also contains recommendations on how to limit exposure to mixtures in the products we use and on how to limit release of mixtures into the environment. Providing brief summaries of each mixture and its effects, Zeliger provides a comprehensive reference, a jumping off point for professionals (with extensive chapter bibliographies) and an introduction to the topic for those studying traditional toxicology. Addressing many inadequately understood illnesses and conditions such as asthma, infertility and cancer, it will also be of interest to health professionals, environmental scientists and lawyers. • Presents a theoretical framework for predicting the effects of chemical mixtures for which no specific data exists (this predictive aspect is important due to the vast number of different potential chemical combinations – far too many to comprehensively catalog). • A quick and convenient source of hard to come by data on the rapidly developing field of chemical mixtures, for groups including chemists and engineers, toxicologists, health professionals and environmental scientists. • New and updated material comprises over 30% of this timely new edition, which includes the latest research data alongside an expanded introduction to the science and art of predicting the toxicological properties of chemical mixtures. Human Toxicology of Chemical Mixtures 4 Copyright Page 5 Contents 8 Preface to the Second Edition 10 Preface to the First Edition 12 List of Abbreviations 14 Part I. Introduction to Chemical Toxicology of Mixtures 18 Chapter 1. Introduction 20 References 23 Chapter 2. Health Effects of Exposures to Chemical Mixtures 24 2.1 Traditional Toxicology 24 2.2 Unexplained Effects of Mixtures 26 2.3 Lipophiles and Hydrophiles 27 2.4 Octanol:Water Partition Coefficients 28 2.5 Summary 29 References 29 Chapter 3. Absorption of Chemical Mixtures 32 3.1 Introduction 32 3.2 Permeability of Mucous Membranes and Octanol:Water Partition Coefficients 32 3.3 Absorption Enhancers 34 3.4 Absorption of Organic Molecules from Aqueous Solutions 35 3.5 Summary 35 References 36 Chapter 4. Chemical Toxicology 38 4.1 Introduction 39 4.2 Toxicology 39 4.3 Molecular Toxicology 40 4.4 Exposure 40 4.5 Absorption 41 4.6 Distribution 41 4.7 Metabolism 42 4.8 Factors Affecting Metabolism of Xenobiotics 44 4.9 Oxidative Stress 48 4.10 Receptor–Xenobiotic Interactions 50 4.11 Endocrine Disruptors 51 4.12 Immunotoxicology 53 4.13 Multiple Site Responses 56 4.14 Mixture Effects 57 References 58 Part II. Exposures to Chemical Mixtures 60 Chapter 5. Scope and Sources of Toxic Exposures 62 5.1 Scope of Exposure: Introduction 62 5.2 Toxic Release 62 5.3 Unknown Toxicities 63 5.4 Proliferation 64 References 65 Chapter 6. In Utero Exposure 66 6.1 Fetal Sensitivity 66 6.2 Toxic Chemicals in the Blood of Newborns 66 6.3 Toxic Hazards of Fetal Toxicants 67 6.4 Mixtures 68 Reference 68 Chapter 7. Air Pollution 70 7.1 Introduction 70 7.2 Pervasive Air Pollutants 71 7.3 Chemical Reactions in the Air 71 7.4 Confined Air Pollutants 74 7.5 Air Pollution in the Breathing Zone 75 7.6 Air Pollution and Health Risk 75 7.7 Mixtures 76 7.8 Particulate Matter 76 7.9 Aerosols 77 7.10 Effects of Nonspecific Origin 78 7.11 Summary 78 References 78 Chapter 8. Water Pollution 82 8.1 Introduction 83 8.2 Mining 83 8.3 Manufacturing 84 8.4 Farming 84 8.5 Power Production 86 8.6 Urban Runoff 87 8.7 Home and Personal Care Products 88 8.8 Priority Water Pollutants 91 8.9 Chemical Reactions in Water 95 8.10 Drinking Water Contaminants in the United States 97 8.11 Mixtures 104 8.12 Toxic Landfill Runoff 107 8.13 Summary 108 References 108 Chapter 9. Soil Pollution 114 9.1 Introduction 114 9.2 Depressed Microbial Activity 115 9.3 Toxicity to Soil-Dwelling Animals 115 9.4 Plant Absorption of Soil Toxins and Bioaccumulation 116 9.5 Effects of Mixtures 116 9.6 Summary 118 References 118 Chapter 10. Food 122 10.1 Introduction 123 10.2 Persistent Organic Pollutants 124 10.3 Mercury 124 10.4 Antibiotics in Meat 125 10.5 Steroids in Meat 125 10.6 Additives in Commercial Food Preparation 126 10.7 Chemical Impurities in Food: Allowable Xenobiotics 127 10.8 Flavor Additives 128 10.9 Artificial Food Colors 130 10.10 Flavor Enhancers: MSG 130 10.11 Aspartame: Non-Nutritive Sweetener 130 10.12 Non-Nutritive Chemicals in Food 131 10.13 The Bread We Eat 131 10.14 VOCs in Food 132 10.15 Chemicals in Food Packaging 133 10.16 Irradiated Food 136 10.17 Toxic Mixtures in Food 136 10.18 Excipients in Pharmaceuticals and Vitamin and Mineral Preparations 138 10.19 Summary 140 References 141 Chapter 11. Chemicals In and Around the Home 146 11.1 Introduction 146 11.2 Arts and Crafts 147 11.3 Automobiles and Small Engines 148 11.4 Cleaners and Fresheners 149 11.5 Maintenance Materials 150 11.6 Brominated Flame Retardants 151 11.7 Personal Care and Cosmetic Products 152 11.8 Pesticides 156 11.9 Other Mixture-Containing Products 156 11.10 Summary 156 References 157 Chapter 12. Sick Building Syndrome 160 12.1 Introduction 160 12.2 SBS Symptoms 161 12.3 Contributory Sources of SBS 161 12.4 VOCs in Buildings 162 12.5 Paint 162 12.6 Environmental Tobacco Smoke 164 12.7 Carpets 164 12.8 Formaldehyde 167 12.9 Other Sources of SBS Toxic Chemicals 168 12.10 Biological Causes of SBS 170 12.11 Mixtures 171 12.12 Investigating an SBS Incident 171 12.13 Summary 173 References 173 Chapter 13. Industrial Exposure 176 13.1 Introduction 176 13.2 Single Chemical Toxicities 177 13.3 Mixture Toxicities 178 13.4 Noise, Organic Solvents, and Hearing 179 13.5 Foundry Fumes and Cancer 179 13.6 Painting and CNS Effects 179 13.7 Printers’ CNS and Mucous Membrane Effects 180 13.8 High Cancer Rates in Road Pavers and Roofers 180 13.9 Nail Salon Work and CNS Effects 180 13.10 Coke Oven Work and Smoking Synergism 180 13.11 Incinerator Fly Ash Toxicity 181 13.12 Naval Divers’ Cancer Cluster 181 13.13 Industrial Solid Waste and Municipal Waste Leachate 181 13.14 Exposures of Workers to Aromatic Hydrocarbons 182 13.15 Polyhalogenated Aromatic Compounds 183 13.16 Color Vision Impairment in Workers 183 13.17 Irradiated Mail Sensitivity 183 13.18 “Aerospace Syndrome” 184 13.19 Hospital Histology Technicians 184 13.20 Persistent Toxic Chemical Compounds 184 13.21 Regional Impact Assessment 185 13.22 Summary 186 References 186 Chapter 14. Pesticides 190 14.1 Introduction 190 14.2 Definitions 191 14.3 Human Toxicities of Pesticides 191 14.4 Toxicity of Pesticide Mixtures 193 14.5 Inert Ingredients in Pesticides 196 14.6 Low-Level Pesticide Poisonings 197 14.7 Summary 199 References 200 Chapter 15. Alcohol and Tobacco: Recreational Toxins 204 15.1 Introduction 204 15.2 Ethanol: Introduction 205 15.3 Mechanisms of Ethanol Mixture Toxicity 205 15.4 Effect of Ethanol on Nutrients and Drugs 206 15.5 Toxicity of Ethanol Mixtures with Other Chemicals 206 15.6 Ethanol and Cancer 209 15.7 Tobacco Toxicity: Introduction 209 15.8 Tobacco and Cancer 211 15.9 Tobacco Smoke Mixtures 211 15.10 Tobacco Smoke Mixtures and Lung Cancer 212 15.11 Noncarcinogenic Tobacco Smoke Synergism 213 15.12 Summary 215 References 215 Chapter 16. Electromagnetic Radiation and Toxic Exposure 222 16.1 Introduction 222 16.2 The Electromagnetic Spectrum 223 16.3 Ionizing Radiation and Toxic Chemical Mixtures 223 16.4 UV Radiation and Toxic Chemical Mixtures 224 16.5 Nonionizing Radiation Introduction 228 16.6 RF Radiation and Toxic Chemical Mixtures 228 16.7 ELF Radiation and Toxic Chemical Mixtures 229 16.8 Summary 231 References 231 Part III. Mixture Effects on Body Systems 236 Chapter 17. Respiratory System 238 17.1 Introduction 238 17.2 Respiratory Irritant Mixtures 240 17.3 Respiratory Sensitization Mixtures 245 17.4 Asthma and Chemical Mixtures 247 17.5 Reactive Airways Dysfunction Syndrome 250 17.6 Respiratory Carcinogens 253 17.7 Unanticipated Respiratory Effects of Chemical Mixtures 254 17.8 Summary 261 References 261 Chapter 18. Nervous System 268 18.1 Introduction 269 18.2 Neurotoxic Chemicals 270 18.3 Indicators and Symptoms of Neurotoxic Poisoning 272 18.4 Mechanisms of Neurotoxic Action 274 18.5 Neurodegenerative Diseases and Toxic Chemical Exposures 274 18.6 Neurotoxicity of Chemical Mixtures 276 18.7 Case Studies: Neurotoxic Chemical Mixtures 282 18.8 Summary 289 References 289 Chapter 19. Developmental Neurotoxicology 298 19.1 Introduction 298 19.2 Mixture Neurotoxicity 298 19.3 Summary 302 References 302 Chapter 20. Autism: Effect of Maternal Exposure to Neurotoxic Chemicals 304 20.1 Autism 304 20.2 Chemical Mixtures 306 20.3 Summary 310 References 311 Chapter 21. Attention Deficit Hyperactivity Disorder 316 21.1 Introduction 316 21.2 Prevalence of ADHD 316 21.3 Environmental Factors in ADHD 318 21.4 Chemical Mixtures as Triggers for ADHD 319 21.5 Summary 321 References 321 Chapter 22. Endocrine System 324 22.1 Introduction 324 22.2 Endocrine-Disrupting Chemicals 325 22.3 Diabetes and EDCs 327 22.4 Breast Cancer and Endocrine Disruptors 328 22.5 Mixture Effects on Endocrine Function: Case Studies 331 22.6 Tobacco Smoke 333 22.7 Summary 333 References 334 Chapter 23. Toxic Infertility 340 23.1 Introduction 341 23.2 Xenobiotics and Female Infertility 341 23.3 Smoking and Female Fertility 343 23.4 Chemically Induced SAB 344 23.5 Xenobiotics and Male Infertility 347 23.6 Chemicals Affecting Male Infertility 349 23.7 Effects of Chemical Mixtures on Male Fertility 349 23.8 Testicular Dysgenesis Syndrome 352 23.9 Summary 352 References 353 Chapter 24. Teratogens 358 24.1 Introduction 358 24.2 Single Chemical Teratogens 359 24.3 Paternally Transmitted Teratogenic Effects 359 24.4 Transgenerational Teratogenic Effects 360 24.5 Teratogenic Mixtures 361 24.6 Summary 367 References 367 Chapter 25. Immune System 372 25.1 Introduction 372 25.2 Immunosuppressants 374 25.3 Immunostimulants 374 25.4 Autoimmune Toxins 375 25.5 Immunotoxic Mixtures 375 25.6 Multiple Chemical Sensitivity (MCS) and Chronic Fatigue Syndrome (CFS) 378 25.7 Summary 378 References 378 Chapter 26. Chemical Sensitivity: Multiple Chemical Sensitivity (MCS), Chronic Fatigue Syndrome (CFS), Fibromyalgia (FM), Gulf War Syndrome 382 26.1 Introduction 382 26.2 Multiple Chemical Sensitivity (MCS) 383 26.3 Chronic Fatigue Syndrome (CFS) 391 26.4 CFS and Chemical Exposure 393 26.5 Fibromyalgia (FM) 394 26.6 Gulf War Syndrome (GWS) 395 26.7 Comorbidity of MCS, CFS, and FM 396 26.8 Chemical Sensitivity Triggers Hypothesis 396 26.9 Summary 399 References 400 Chapter 27. Skin 406 27.1 Introduction 406 27.2 Skin Permeability 406 27.3 Allergic Contact Dermatitis 410 27.4 Dermally Induced Respiratory Hypersensitivity 411 27.5 Chemical Burns 411 27.6 Mixtures 412 27.7 Summary 413 References 413 Chapter 28. Musculoskeletal System 416 28.1 Introduction 416 28.2 Rheumatoid Arthritis 417 28.3 Scleroderma and Systemic Sclerosis 417 28.4 Systemic Lupus Erythematosus 418 28.5 Osteoporosis and Osteomalacia 418 28.6 Mixtures 419 28.7 Summary 420 References 420 Chapter 29. Cardiovascular System 422 29.1 Introduction 422 29.2 Leachates 425 29.3 Air Pollution 425 29.4 Tobacco 428 29.5 Cancer 429 29.6 Summary 429 References 429 Chapter 30. Liver 434 30.1 Introduction 434 30.2 Single Chemical Hepatotoxins 436 30.3 Hepatotoxic Mixtures: Animal Studies 436 30.4 Human Case Studies 438 30.5 Hepatic Cancer 440 30.6 Summary 440 References 440 Chapter 31. Kidneys 444 31.1 Introduction 444 31.2 Single Chemical Renal Toxins 445 31.3 Nephrotoxic Chemical Mixtures 446 31.4 Summary 447 References 447 Chapter 32. Cancer 450 32.1 Introduction 451 32.2 Cancer Incidence Rates 451 32.3 Chemical Carcinogens 452 32.4 Mechanisms of Carcinogenesis 456 32.5 Single Chemical Carcinogens 461 32.6 Occupational Exposures Known To Be Carcinogenic 462 32.7 Mixture Exposures Known To Be Carcinogenic—Many Component Mixtures 463 32.8 Mixture Exposures Known To Be Carcinogenic—Two-Component Mixtures 473 32.9 Tobacco and Cancer 474 32.10 Summary and Outlook 475 References 476 Chapter 33. Cancer Clusters 484 33.1 Introduction 484 33.2 Mixture-Induced Cancer Clusters 485 33.3 Summary 492 References 492 Chapter 34. Nanotoxicology 496 34.1 Introduction 496 34.2 Nanoparticles 497 34.3 NP Uptake 498 34.4 Mechanisms of Toxic Effects of NPs: OS 498 34.5 Case Studies: NP Mixtures 499 34.6 Summary 501 References 501 Chapter 35. Children 504 35.1 Introduction 504 35.2 In Utero Exposure 505 35.3 Air Pollution 508 35.4 Water Pollution 508 35.5 Food 508 35.6 Chemicals in the Home 509 35.7 Sick-Building Chemical Exposure 510 35.8 Industrial Exposure 511 35.9 Farming: Pesticides 511 35.10 Tobacco Smoke 511 35.11 Asthma 512 35.12 Neurodevelopmental Disorders and Teratogenic Effects 513 35.13 Children and Global Warming 513 35.14 Childhood Cancer 514 References 514 Chapter 36. Childhood Cancer 516 36.1 Childhood Cancer 516 36.2 Prevalent Childhood Cancers 517 36.3 Childhood Cancer Studies 517 36.4 Children’s Cancer Clusters 519 36.5 Summary 521 References 521 Chapter 37. Toxicology of Global Warming 524 37.1 Introduction 524 37.2 Global Warming and Human Disease 525 37.3 Extreme Climatic Events 526 37.4 Air Pollution 527 37.5 Water Pollution 529 37.6 Toxic Chemicals and Thermal Stress 532 37.7 Summary 533 References 533 Part IV. Regulatory Requirements, Conclusions 538 Chapter 38. Regulatory Requirements 540 38.1 Introduction 540 38.2 Warning Requirements 540 38.3 Warning Deficiencies 541 38.4 Warnings for Multiple Exposures 542 38.5 Warnings for Mixtures 542 38.6 Odor 543 38.7 Warning Recommendations 543 38.8 Summary 546 References 547 Chapter 39. Conclusions and Recommendations 548 39.1 Introduction 548 39.2 Conclusions 548 39.3 Recommendations 550 39.4 The Future 551 References 551 Index 554 9781437734638 Elsevier LTD.