Human Toxicology of Chemical Mixtures, Second Edition

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. Front matter......Page 2 Copyright......Page 4 Dedication......Page 5 Preface to the Second Edition......Page 6 Preface to the First Edition......Page 7 List of Abbreviations......Page 9 1 Introduction......Page 12 References......Page 15 2.1.1 Additivity......Page 16 2.1.5 Sequential Effects......Page 17 2.2 Unexplained Effects of Mixtures......Page 18 2.3 Lipophiles and Hydrophiles......Page 19 2.4 Octanol:Water Partition Coefficients......Page 20 References......Page 21 3.2 Permeability of Mucous Membranes and Octanol:Water Partition Coefficients......Page 23 3.3 Absorption Enhancers......Page 25 3.5 Summary......Page 26 References......Page 27 4 Chemical Toxicology......Page 28 4.2 Toxicology......Page 29 4.4 Exposure......Page 30 4.6 Distribution......Page 31 4.7 Metabolism......Page 32 4.8 Factors Affecting Metabolism of Xenobiotics......Page 34 4.8.5 Hormones......Page 35 4.8.9 Inhibition......Page 36 4.8.11 Dose and Timing......Page 37 4.9 Oxidative Stress......Page 38 4.9.1 Electromagnetic Radiation......Page 39 4.10 Receptor–Xenobiotic Interactions......Page 40 4.11.1 Effects on Humans......Page 41 4.11.2 Endocrine-Disrupting Chemicals......Page 42 4.12 Immunotoxicology......Page 43 4.12.1 Immunosuppression......Page 44 4.12.2 Immunostimulation......Page 45 4.13 Multiple Site Responses......Page 46 4.14 Mixture Effects......Page 47 References......Page 48 5.2 Toxic Release......Page 50 5.3 Unknown Toxicities......Page 51 5.4 Proliferation......Page 52 References......Page 53 6.2 Toxic Chemicals in the Blood of Newborns......Page 54 6.3 Toxic Hazards of Fetal Toxicants......Page 55 Reference......Page 56 7.1 Introduction......Page 57 7.3 Chemical Reactions in the Air......Page 58 7.4 Confined Air Pollutants......Page 61 7.6 Air Pollution and Health Risk......Page 62 7.8 Particulate Matter......Page 63 7.9 Aerosols......Page 64 References......Page 65 8 Water Pollution......Page 68 8.2 Mining......Page 69 8.4 Farming......Page 70 8.4.3 Nutrients......Page 71 8.5.1 Petroleum Production and Refining......Page 72 8.6 Urban Runoff......Page 73 8.7.2 Cosmetics......Page 74 8.7.7 Medicines......Page 75 8.7.9 Paint and Paint Products......Page 76 8.8 Priority Water Pollutants......Page 77 8.9.2 Disinfection By-Products......Page 81 8.10 Drinking Water Contaminants in the United States......Page 83 8.11 Mixtures......Page 90 8.12 Toxic Landfill Runoff......Page 93 References......Page 94 9.1 Introduction......Page 99 9.3 Toxicity to Soil-Dwelling Animals......Page 100 9.5 Effects of Mixtures......Page 101 References......Page 103 10 Food......Page 106 10.1 Introduction......Page 107 10.3 Mercury......Page 108 10.5 Steroids in Meat......Page 109 10.6 Additives in Commercial Food Preparation......Page 110 10.7 Chemical Impurities in Food: Allowable Xenobiotics......Page 111 10.8 Flavor Additives......Page 112 10.11 Aspartame: Non-Nutritive Sweetener......Page 114 10.13 The Bread We Eat......Page 115 10.14 VOCs in Food......Page 116 10.15 Chemicals in Food Packaging......Page 117 10.17.2 Genotoxic Food Additives......Page 120 10.17.7 Enzyme Inhibition......Page 121 10.18.1 Sulfites......Page 122 10.18.5 Propylene Glycol......Page 123 10.19 Summary......Page 124 References......Page 125 11.1 Introduction......Page 130 11.2 Arts and Crafts......Page 131 11.3 Automobiles and Small Engines......Page 132 11.4 Cleaners and Fresheners......Page 133 11.5 Maintenance Materials......Page 134 11.6 Brominated Flame Retardants......Page 135 11.7 Personal Care and Cosmetic Products......Page 136 11.10 Summary......Page 140 References......Page 141 12.1 Introduction......Page 144 12.3 Contributory Sources of SBS......Page 145 12.5 Paint......Page 146 12.7 Carpets......Page 148 12.8 Formaldehyde......Page 151 12.9.4 Dioxins in Wood Preservatives......Page 152 12.9.7 Radon, Asbestos, and Tobacco Smoke......Page 153 12.10.3 Animal Allergens......Page 154 12.12 Investigating an SBS Incident......Page 155 References......Page 157 13.1 Introduction......Page 160 13.2 Single Chemical Toxicities......Page 161 13.3 Mixture Toxicities......Page 162 13.6 Painting and CNS Effects......Page 163 13.10 Coke Oven Work and Smoking Synergism......Page 164 13.13 Industrial Solid Waste and Municipal Waste Leachate......Page 165 13.14 Exposures of Workers to Aromatic Hydrocarbons......Page 166 13.17 Irradiated Mail Sensitivity......Page 167 13.20 Persistent Toxic Chemical Compounds......Page 168 13.21 Regional Impact Assessment......Page 169 References......Page 170 14.1 Introduction......Page 173 14.3 Human Toxicities of Pesticides......Page 174 14.4 Toxicity of Pesticide Mixtures......Page 176 14.5 Inert Ingredients in Pesticides......Page 179 14.6 Low-Level Pesticide Poisonings......Page 180 14.7 Summary......Page 182 References......Page 183 15.1 Introduction......Page 186 15.3 Mechanisms of Ethanol Mixture Toxicity......Page 187 15.5 Toxicity of Ethanol Mixtures with Other Chemicals......Page 188 15.7 Tobacco Toxicity: Introduction......Page 191 15.9 Tobacco Smoke Mixtures......Page 193 15.10.4 Smoking and Radon......Page 194 15.11.6 Smoking and Organic Solvent Exposure......Page 195 15.11.7 Smoking and Alcohol Abuse......Page 196 References......Page 197 16.1 Introduction......Page 203 16.3 Ionizing Radiation and Toxic Chemical Mixtures......Page 204 16.4 UV Radiation and Toxic Chemical Mixtures......Page 205 16.6 RF Radiation and Toxic Chemical Mixtures......Page 209 16.7 ELF Radiation and Toxic Chemical Mixtures......Page 210 References......Page 212 17.1 Introduction......Page 216 17.2 Respiratory Irritant Mixtures......Page 218 17.3 Respiratory Sensitization Mixtures......Page 223 17.4 Asthma and Chemical Mixtures......Page 225 17.5 Reactive Airways Dysfunction Syndrome......Page 228 17.6 Respiratory Carcinogens......Page 231 Case 1 [83]......Page 232 Case 4 [103]......Page 233 Case 6 [8]......Page 234 Case 9 [91]......Page 235 Case 11 [9]......Page 236 Case 12 [82]......Page 237 Case 14 [105]......Page 238 References......Page 239 18 Nervous System......Page 245 18.1 Introduction......Page 246 18.2 Neurotoxic Chemicals......Page 247 18.3 Indicators and Symptoms of Neurotoxic Poisoning......Page 249 18.5.1 Parkinson’s Disease......Page 251 18.5.4 Multiple Sclerosis......Page 252 18.6.1 Pesticide Mixtures......Page 253 18.6.2 Organic Solvent Mixtures......Page 256 Case 1 [117]......Page 259 Case 3 [119]......Page 260 Site B......Page 261 Case 6 [122]......Page 262 Case 8 [124]......Page 263 Case 11 [128]......Page 264 Case 14 [131]......Page 265 References......Page 266 19.2 Mixture Neurotoxicity......Page 274 References......Page 278 20.1 Autism......Page 280 20.2 Chemical Mixtures......Page 282 20.3 Summary......Page 286 References......Page 287 21.2 Prevalence of ADHD......Page 292 21.3 Environmental Factors in ADHD......Page 294 21.4 Chemical Mixtures as Triggers for ADHD......Page 295 References......Page 297 22.1 Introduction......Page 300 22.2 Endocrine-Disrupting Chemicals......Page 301 22.3 Diabetes and EDCs......Page 303 22.4 Breast Cancer and Endocrine Disruptors......Page 304 22.5 Mixture Effects on Endocrine Function: Case Studies......Page 307 22.7 Summary......Page 309 References......Page 310 23 Toxic Infertility......Page 316 23.2 Xenobiotics and Female Infertility......Page 317 23.3 Smoking and Female Fertility......Page 319 23.4.2 Semiconductor Manufacturing......Page 320 23.4.4 Agricultural Mixtures......Page 321 23.4.9 Formulated Pesticide Use......Page 322 23.5 Xenobiotics and Male Infertility......Page 323 23.5.2 Impaired Spermatogenesis......Page 324 23.7.1 Organic Solvent Mixtures......Page 325 23.7.2 Pesticide Mixture......Page 326 23.7.6 Diesel Exhausts......Page 327 23.9 Summary......Page 328 References......Page 329 24.1 Introduction......Page 334 24.3 Paternally Transmitted Teratogenic Effects......Page 335 24.4 Transgenerational Teratogenic Effects......Page 336 24.5.1 Organic Solvents......Page 337 24.5.3 Pesticides......Page 339 24.5.5 Ethanol Mixtures......Page 340 24.5.6 Air Pollution......Page 341 24.5.8 Hazardous Waste Site Proximity......Page 342 References......Page 343 25.1 Introduction......Page 347 25.3 Immunostimulants......Page 349 25.5 Immunotoxic Mixtures......Page 350 25.5.5 Tobacco Smoke and Organic Solvents......Page 351 25.5.7 Air Pollution......Page 352 References......Page 353 26.1 Introduction......Page 357 26.2 Multiple Chemical Sensitivity (MCS)......Page 358 26.2.1 MCS Symptoms......Page 360 26.2.2 Causative MCS Chemicals......Page 361 William J. Rea......Page 362 Iris R. Bell......Page 363 Martin L. Pall......Page 364 26.2.4 MCS Mixture Effect......Page 365 26.3 Chronic Fatigue Syndrome (CFS)......Page 366 26.4 CFS and Chemical Exposure......Page 368 26.5 Fibromyalgia (FM)......Page 369 26.6 Gulf War Syndrome (GWS)......Page 370 26.8 Chemical Sensitivity Triggers Hypothesis......Page 371 26.9 Summary......Page 374 References......Page 375 27.2 Skin Permeability......Page 380 27.3 Allergic Contact Dermatitis......Page 384 27.5 Chemical Burns......Page 385 27.6 Mixtures......Page 386 References......Page 387 28.1 Introduction......Page 390 28.3 Scleroderma and Systemic Sclerosis......Page 391 28.5 Osteoporosis and Osteomalacia......Page 392 28.6 Mixtures......Page 393 References......Page 394 29.1 Introduction......Page 396 29.3 Air Pollution......Page 399 29.4 Tobacco......Page 402 References......Page 403 30.1 Introduction......Page 407 30.3 Hepatotoxic Mixtures: Animal Studies......Page 409 30.4 Human Case Studies......Page 411 References......Page 413 31.1 Introduction......Page 416 31.2 Single Chemical Renal Toxins......Page 417 31.3 Nephrotoxic Chemical Mixtures......Page 418 References......Page 419 32 Cancer......Page 421 32.2 Cancer Incidence Rates......Page 422 32.3 Chemical Carcinogens......Page 423 32.4 Mechanisms of Carcinogenesis......Page 427 32.5.4 1,3-Butadiene......Page 432 32.6 Occupational Exposures Known To Be Carcinogenic......Page 433 32.7 Mixture Exposures Known To Be Carcinogenic—Many Component Mixtures......Page 434 32.7.3 PAH Exposure and Cancer......Page 435 32.7.4 Painters......Page 436 32.7.7 Oil Refinery and Petrochemical Workers......Page 437 32.7.8 Hazardous Waste Sites and Water Pollution......Page 438 32.7.11 Leather Tanning Industry......Page 439 32.7.12 Pesticides......Page 440 32.7.13 Hematolymphopoietic Malignancies......Page 442 32.8 Mixture Exposures Known To Be Carcinogenic—Two-Component Mixtures......Page 444 32.9 Tobacco and Cancer......Page 445 32.10 Summary and Outlook......Page 446 References......Page 447 33.1 Introduction......Page 454 33.2.2 Cluster 2: Prostate Cancer......Page 455 33.2.4 Cluster 7: Brain Cancer Cluster—Electronic Workers......Page 456 33.2.6 Cluster 9: Brain Cancers in Offspring of Electronic Workers......Page 457 33.2.9 Cluster 12: Multiple Cancer Cluster......Page 458 33.2.11 Cluster 14: Childhood Leukemia......Page 459 33.2.12 Cluster 15: Multiple Cancer Clusters......Page 460 33.2.13 Cluster 16: Toxic Waste Disposal Site-Related Clusters......Page 461 References......Page 462 34.1 Introduction......Page 465 34.2.3 Anthropogenic: Intentional NPs......Page 466 34.4 Mechanisms of Toxic Effects of NPs: OS......Page 467 34.5.2 Cardiovascular Disease......Page 468 34.5.3 Respiratory Disease......Page 469 References......Page 470 35.1 Introduction......Page 473 35.2 In Utero Exposure......Page 474 35.2.1 Toxic Hazards of Fetal Toxicants......Page 475 35.5 Food......Page 477 35.6 Chemicals in the Home......Page 478 35.7 Sick-Building Chemical Exposure......Page 479 35.10 Tobacco Smoke......Page 480 35.11 Asthma......Page 481 35.13 Children and Global Warming......Page 482 References......Page 483 36.1 Childhood Cancer......Page 485 36.3.2 Solvents......Page 486 36.4.2 Cluster 2: Childhood Leukemia......Page 488 36.4.3 Brain Cancers in Offspring of Electronic Workers......Page 489 References......Page 490 37.1 Introduction......Page 492 37.2 Global Warming and Human Disease......Page 493 37.3.1 Hurricanes......Page 494 37.4 Air Pollution......Page 495 37.5 Water Pollution......Page 497 37.6 Toxic Chemicals and Thermal Stress......Page 500 References......Page 501 38.2 Warning Requirements......Page 505 38.3 Warning Deficiencies......Page 506 38.5 Warnings for Mixtures......Page 507 38.7 Warning Recommendations......Page 508 38.8 Summary......Page 511 References......Page 512 39.2 Conclusions......Page 513 39.3 Recommendations......Page 515 References......Page 516 Index......Page 518