Formaldehyde is virtually ubiquitous in the modern environment due to its cost-effective nature, its use in resin formation, and its preservative properties. Though formaldehyde is necessary for many products and processes important to the world's economy, this economic dependence on formaldehyde comes at a cost to public health. Growth and consequent industrialization rely heavily on formaldehyde use. New buildings—residences, public places, and offices—are not only built with timber preserved by formaldehyde, but they are also furnished with wood, wool, and textile products that contain formaldehyde. The general population faces environmental exposure from indoor and outdoor air pollution, food, and even medicine. Scientific inquiry into formaldehyde exposure has grown in response. This book consolidates the new and established body of formaldehyde research in the scholarly community, focusing on exposure, genotoxicity, and adverse health outcomes. Through this resource, we hope to increase awareness of the broad range of health effects posed by formaldehyde exposure, and to encourage interdisciplinary interest, as well as research, into this pervasive compound—especially in the United States and China, where formaldehyde production and usage is high. This book will be useful to researchers of environmental and occupational exposure, students, and government regulators and anyone exposed to formaldehyde in the workplace and/or at home.
Author(s): Luoping Zhang
Series: Issues In Toxicology Vol. 37
Publisher: Royal Society Of Chemistry
Year: 2018
Language: English
Pages: 414
Tags: Formaldehyde: Toxicology, Formaldehyde: Toxicity, Public Health & Preventive Medicine
Front Cover......Page 1
Formaldehyde: Exposure, Toxicity and Health Effects......Page 2
Preface......Page 8
Acknowledgements......Page 10
Dedication......Page 14
Contents......Page 16
1.1 Formaldehyde—The Origins of Life on Earth......Page 26
1.2.1 Endogenous Production of Formaldehyde......Page 27
1.2.2 Exogenous Synthesis of Formaldehyde......Page 28
1.3 Industrial Uses of Formaldehyde......Page 29
1.5 Global Economic Significance of Formaldehyde......Page 30
1.5.1 Production Capacity and Output......Page 31
1.5.2 Consumption and Distribution......Page 33
1.6.3 Hurricanes Katrina and Rita......Page 36
1.7 Controversial and Neglected Issues in Formaldehyde Studies......Page 37
1.7.2 US and China Focus......Page 38
1.8 Conclusion......Page 39
References......Page 40
2.1 Occupational Exposure and Regulation......Page 45
2.2 Indoor Air Exposure......Page 49
2.3 Outdoor Air Exposure......Page 53
2.5 Metabolism and Fate of Formaldehyde......Page 54
Acknowledgements......Page 56
References......Page 57
3.1 Formaldehyde Regulation......Page 64
3.2.2.1 Residential Exposure......Page 67
3.2.3 Outdoor Exposure......Page 72
3.3 Estimated Personal Exposure......Page 78
3.4 Conclusion......Page 80
References......Page 81
4.1.1 Acute Poisoning......Page 88
4.1.4 Worldwide Case Reports......Page 89
4.2.1 Neurotoxicity......Page 90
4.2.3 Allergic Asthma and Immune System Effects......Page 91
4.3.1 Blood Formation via Hematopoiesis......Page 92
4.3.2 Reduced Blood Cell Counts......Page 93
4.3.4 Altered Lymphocyte Subsets......Page 95
4.3.5 Hematotoxicity Studies in Animals......Page 96
4.4.1 DNA–Protein Crosslinks (DPCs)......Page 98
4.4.2 DNA–Protein Crosslink Repair in Yeast......Page 100
4.4.3 DNA Damage and Repair via the FANC–BRCA Pathway......Page 101
4.4.4 DNA Adducts......Page 104
4.4.5 Cytogenetic Alterations......Page 105
4.5 Functional Toxicogenomic Profiling and Epigenomic Alterations......Page 106
4.6 Summary of Formaldehyde Induced Toxicities......Page 107
Acknowledgements......Page 108
References......Page 109
5.1.1 Nasopharyngeal Cancer......Page 121
5.1.3 Leukemia and Blood Cancers......Page 123
5.2 Cancer Studies in China......Page 124
5.3.1 Importance of Carcinogen Classification......Page 125
5.3.2.3 OEHHA......Page 126
5.3.3.1 NTP Primary Classification......Page 127
5.3.3.5 Updated NTP Classification......Page 128
5.4.1 Can Formaldehyde Reach the Target Bone Marrow......Page 129
5.4.1.3 Potential Systemic Effects of Formaldehyde......Page 130
5.4.2 Formaldehyde-induced Hematotoxicity and Stem Cell Toxicity......Page 131
5.4.2.2 Animal Studies......Page 132
5.5 Formaldehyde Carcinogenicity Summary......Page 133
References......Page 134
6.1 Epidemiological Findings of Formaldehyde and Leukemia......Page 141
6.1.1 Classic Epidemiological Studies of Formaldehyde......Page 142
6.2 Meta-analysis Approach......Page 143
6.2.1 Novel Study Design to Better Address Key Questions......Page 144
6.2.2 Collection and Selection of Epidemiological Studies......Page 145
6.3.1 Meta-analysis Results......Page 147
6.4 Results from Updated Meta-analysis......Page 149
6.5.1 Overview of the Results from Six Meta-analyses......Page 151
6.5.2 Comparison of Novel Approach with Traditional Meta-analyses......Page 153
6.5.3 Risk Varies in Industrial Workers vs. Professionals......Page 154
6.6 Summary and Conclusions......Page 156
References......Page 161
7.1 Overview of Leukemogenesis......Page 166
7.1.1 Leukemic Stem Cell Theory......Page 167
7.1.2 Chemically Induced Leukemias......Page 168
7.2 Targeting Hematopoietic Stem/Progenitor Cells......Page 169
7.2.1 Culturing of Myeloid Progenitor Cells......Page 170
7.2.2 Findings in Circulating Myeloid Progenitor Colony Cells of Exposed Workers......Page 171
7.2.4 Formaldehyde Suppressed Myeloid Progenitor Cells in Murine Bone Marrow......Page 172
7.3 Models of Formaldehyde-induced Leukemia......Page 174
7.3.1 Traditional Model: Targeting Bone Marrow Hematopoietic Stem Cells......Page 176
7.3.2 Alternative Model 1: Targeting Blood Stem Cells and Progenitors......Page 177
7.3.3 Alternative Model 2: Targeting Pluripotent Nasal/Oral Stem Cells......Page 178
7.3.4 Alternative Model 3: Targeting Hematopoietic Stem and Progenitor Cells in the Lungs......Page 179
7.4.1 Does Formaldehyde Induce Bone Marrow Toxicity and by Which Mechanisms......Page 180
7.4.2 Does Formaldehyde Induce Hematotoxicity and Stem Cell Toxicity......Page 182
7.4.3 Can Formaldehyde Damage Pluripotent Hematopoietic Stem Cells in the Nose and Lungs......Page 183
Acknowledgements......Page 184
References......Page 185
Chapter 8 - Formaldehyde Induced Leukemia-specific Chromosomal Aneuploidy......Page 193
8.2.1 Identification of Study Factories and Subjects......Page 194
8.2.3Exposure Assessment......Page 195
8.2.4 Biological Sampling and Physical Examination......Page 197
8.2.5 Preparing Metaphase from Cultured CFU–GM Cells......Page 198
8.3.2 A Priori Hypothesis Tested in Benzene-exposed Workers......Page 199
8.3.3 FISH Application in CFU–GM Progenitor Cells......Page 200
8.3.4 Implication of the Initial Findings......Page 202
8.4.2 Study Subjects Selected in CWAS......Page 203
8.5.1 Loss of Chromosomes (Monosomy)......Page 205
8.5.2.3 Implications of Findings in Chromosome Gains......Page 207
8.5.4 Comparison with Other Chemically-induced AML/MDS......Page 208
8.6.1 Formaldehyde-induced Chromosomal Aneuploidy in Myeloid Progenitor Cells......Page 209
8.6.2 Potential Mechanisms of Formaldehyde-induced Aneuploidy......Page 210
Acknowledgements......Page 211
References......Page 212
9.1 The Basics on Brain Tumors......Page 217
9.2.1 Questionnaire-based Traditional Epidemiology......Page 218
9.3 Epidemiologic Studies of Formaldehyde and Brain Tumors......Page 220
9.3.1.1 Pathologists & Anatomists......Page 221
9.3.2 Brain Cancer Risk Among Industrial Workers......Page 226
9.4.1 Study Design and Exposure Information......Page 227
9.4.3 Comparison and Discussion of Both Meta-analyses......Page 230
9.5 Summary and Discussion......Page 231
References......Page 233
10.1 Introduction and Importance......Page 236
10.3 Association Between Formaldehyde Exposure and ALS......Page 237
10.3.2 NIEHS Case–Control Study......Page 238
10.3.5 NIEHS— Sweden Study......Page 241
10.4.1 Parkinson’s Disease......Page 242
10.4.2 Alzheimer’s Disease......Page 244
10.4.3.1 Connection with Alzheimer’s Disease......Page 245
10.5 Memory, Learning, and Behavioral Effects of Formaldehyde......Page 246
10.5.3 Formaldehyde-laced Drug Abuse......Page 247
10.6.1 Analysis of Neurodegenerative Effects in Animals......Page 248
10.6.2.2 Formaldehyde Metabolism......Page 251
10.6.3 Potential Mechanisms and Contributors to Neurodegeneration......Page 252
Acknowledgements......Page 256
References......Page 257
11.1 Formaldehyde Exposure in Children......Page 265
11.1.1 Routes of Exposure......Page 266
11.1.3.1 In utero Exposure (Conception to Birth)......Page 268
11.1.3.2 Early-life Exposure (0–5 Years Old)......Page 269
11.1.3.4 Exposure in Teenagers (13–19 Years Old)......Page 270
11.1.3.5 Young Adults (20–26 Years Old)......Page 271
11.2 Formaldehyde-associated Biomarkers and Health Outcomes......Page 272
11.2.1 Asthma-specific Markers......Page 276
11.2.2 Immuno-markers and Adverse Health Outcomes......Page 277
11.2.3 Cytogenetic Biomarkers and Associated Health Outcomes......Page 278
11.2.4 Childhood Leukemia and Cancer Risk......Page 279
11.2.6 Challenges of Studies in Children......Page 281
11.3.1 Formaldehyde Regulation in Children......Page 282
11.3.2 Johnson & Johnson's Reformulation......Page 283
Acknowledgements......Page 284
References......Page 285
12.1 Background......Page 290
12.2.1.2 Population Studies......Page 291
12.2.2.2 Female Fertility......Page 292
12.2.2.3 Male Reproductivity......Page 298
12.2.3 Spontaneous Abortion Studies......Page 299
12.2.4.1 Congenital Anomalies......Page 301
12.2.4.2 Low Birth Weight......Page 303
12.2.5 NIOSH Study......Page 304
12.3 Human Study Challenges......Page 305
12.4.2 Novel Approach in Updated Meta-analysis......Page 306
12.4.3 Major Findings of the Updated Meta-analysis......Page 307
12.4.4 Comparison of Results Between Both Meta-analyses......Page 312
Acknowledgements......Page 314
References......Page 315
13.1 Overview of Experimental Animal Studies......Page 318
13.2.1 Reproductive Toxicity in Rats......Page 326
13.2.3 Reproductive Toxicity in Other Animal Models......Page 327
13.3.1 Developmental Toxicity in Rats......Page 328
13.3.3 Developmental Toxicity in Other Animal Models......Page 329
13.5 Animal Studies in ex vivo and in vitro......Page 330
13.6 Summary......Page 331
References......Page 332
14.1 Overview of Mechanisms of Toxicity in the Reproductive System......Page 336
14.3 Formaldehyde-induced Oxidative Stress......Page 337
14.4 Alternative Mechanisms of Action......Page 338
14.4.3 Formaldehyde-induced Apoptosis......Page 339
14.4.6 Stress Related Outcomes......Page 340
14.5 Reproductive Toxicity Induced by Other Chemicals Compared to Formaldehyde......Page 341
14.6 Summary......Page 342
References......Page 343
15.1.1 Exposure Types and Sources......Page 349
15.1.2 Exposure Routes in Adults and Children......Page 351
15.1.3 Regulation of Formaldehyde Exposure......Page 352
15.2.1 Acute and Chronic Toxicity......Page 353
15.2.3 Hematotoxicity......Page 354
15.2.5 Reproductive Toxicity......Page 355
15.3.2 Formaldehyde Associated Leukemias......Page 356
15.3.5 Health Effects in Children......Page 357
15.4.2 Controversy and Challenges of Formaldehyde Research......Page 358
15.4.3 Recommendations Suggested for Future Formaldehyde Research......Page 359
References......Page 361
Appendix 1 - Abbreviations......Page 367
Appendix 2 - Glossary......Page 372
Appendix 3 - Meta-analysis Methods......Page 382
Appendix 4 - Statistical Methods Appliedand Supplementary Data (Chapter 8)......Page 394
Appendix 5 - Figure Index......Page 400
Appendix 6 - Table Index......Page 404
Subject Index......Page 407
