Flora Handbook of Arsenic Toxicology

1. Auflage 2014
ISBN: 978-0-12-419955-2
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 752 Seiten

Throughout history, arsenic has been used as an effective and lethal poison. Today, arsenic continues to present a real threat to human health all over the world, as it contaminates groundwater and food supplies. Handbook of Arsenic Toxicology presents the latest findings on arsenic, its chemistry, its sources and its acute and chronic effects on the environment and human health. The book takes readings systematically through the target organs, before detailing current preventative and counter measures. This reference enables readers to effectively assess the risks related to arsenic, and provide a comprehensive look at arsenic exposure, toxicity and toxicity prevention. - Brings together current findings on the effects of arsenic on the environment and human health - Includes state-of-the-art techniques in arsenic toxicokinetics, speciation and molecular mechanisms - Provides all the information needed for effective risk assessment, prevention and countermeasure

Autoren/Hrsg.

Flora, Swaran Jeet Singh

Inhaltsverzeichnis

1;Front Cover;1
2;Handbook of Arsenic Toxicology;4
3;Copyright Page;5
4;Contents;6
5;Foreword;18
6;Preface;20
7;Acknowledgements;24
8;List of Contributors;26
9;1 Arsenic: Chemistry, Occurrence, and Exposure;30
9.1;1.1 Introduction;30
9.2;1.2 Chemistry of Arsenic;31
9.2.1;1.2.1 Origin and History;31
9.2.2;1.2.2 Atomic Structure and Bonding;32
9.2.3;1.2.3 Arsenic Oxidation and Reduction;34
9.2.4;1.2.4 Arsenic Methylation;35
9.2.5;1.2.5 Historical and Modern Applications of Arsenic;36
9.3;1.3 Arsenic Minerals and Compounds;37
9.3.1;1.3.1 Arsenosulfides;37
9.3.2;1.3.2 Metal Arsenides;39
9.3.3;1.3.3 Arsenites;39
9.3.4;1.3.4 Arsenates;40
9.4;1.4 Organoarsenicals;40
9.4.1;1.4.1 Organoarsenicals in the Food Chain;41
9.4.2;1.4.2 Organoarsenicals in Chemical Weapons;42
9.4.3;1.4.3 Methylation in Mammals;42
9.5;1.5 Arsenic Mobilization in the Environment;42
9.5.1;1.5.1 Aqueous Chemistry of Arsenic;43
9.5.2;1.5.2 Redox-Dependent Mobilization of Arsenic;45
9.5.3;1.5.3 Microbial-Dependent Mobilization;45
9.6;1.6 Sources of Arsenic in the Biosphere;45
9.6.1;1.6.1 Arsenic in Rocks and Soils;46
9.6.2;1.6.2 Arsenic in the Atmosphere;48
9.6.2.1;1.6.2.1 Arsenic Emission due to Burning of Coal;49
9.6.2.2;1.6.2.2 Arsenic Dissipation from Fly Ash;49
9.6.3;1.6.3 Arsenic in Various Water Resources;50
9.6.3.1;1.6.3.1 Rain Water;50
9.6.3.2;1.6.3.2 River and Lake Water;50
9.6.3.3;1.6.3.3 Sea and Estuarine Water;51
9.6.3.4;1.6.3.4 Ground Water;51
9.6.4;1.6.4 Arsenic in Dietary Products;52
9.6.4.1;1.6.4.1 Plants and Crops;52
9.6.4.2;1.6.4.2 Rice and Other Food Items;52
9.6.4.3;1.6.4.3 Tobacco;53
9.7;1.7 Arsenic in Hydrothermal and Geothermal Fluids;53
9.7.1;1.7.1 Arsenic Occurrence in Hydrothermal Fluids;53
9.7.2;1.7.2 Arsenic Concentration in Shallow and Deep Hydrothermal Systems;55
9.7.3;1.7.3 Arsenic Occurrence in Geothermal Systems;56
9.7.4;1.7.4 Arsenic Speciation and Deposition in Geothermal Fluids;57
9.7.5;1.7.5 Biogeochemical Fate of Arsenic in Hydro- and Geothermal Systems;58
9.8;1.8 Arsenic Release from Mining and Mineral Processing;58
9.8.1;1.8.1 Oxidation of Arsenic Sulfide and Industrial Ore Leaching;58
9.8.2;1.8.2 Chemistry of Arsenic Within Mining Wastes;60
9.8.3;1.8.3 Arsenic Release by Artisanal Mining;61
9.9;1.9 Global Occurrence of Arsenic in Ground Water;61
9.9.1;1.9.1 Arsenic Release and Mobility in Natural Water;61
9.9.2;1.9.2 Natural and Anthropogenic Occurrence Globally;62
9.9.2.1;1.9.2.1 India, Bangladesh, and Nepal;62
9.9.2.2;1.9.2.2 Latin America;63
9.9.2.3;1.9.2.3 Argentina, Mexico, and Chile;64
9.9.2.4;1.9.2.4 Peru;65
9.9.2.5;1.9.2.5 California;65
9.9.2.6;1.9.2.6 Central America;65
9.10;1.10 Methods of Arsenic Removal from Water;66
9.10.1;1.10.1 Removal via Precipitation;66
9.10.2;1.10.2 Removal via Adsorption;67
9.10.3;1.10.3 Phyto-Remediation;69
9.11;1.11 Conclusions;69
9.12;References;70
10;2 Ground Water Arsenic Contamination and Its Health Effects in Bangladesh;80
10.1;2.1 Introduction;80
10.2;2.2 Arsenic Contamination in Bangladesh Ground Water;81
10.2.1;2.2.1 Reasons for Leaching Arsenic in the Ground Water of Bangladesh;82
10.2.2;2.2.2 Reasons for Variation of Arsenic Concentrations Between the Aquifers;83
10.3;2.3 Extent of Arsenic Contamination in Bangladesh;83
10.4;2.4 Arsenic in Different Environmental Media of Bangladesh;84
10.4.1;2.4.1 Soil;84
10.4.2;2.4.2 River;84
10.4.3;2.4.3 Food Chain;86
10.5;2.5 Health Effects of Arsenic Toxicity in Bangladesh;88
10.6;2.6 Epidemiology of Arsenicosis in Bangladesh;95
10.7;2.7 Management of Arsenicosis Patients in Bangladesh;95
10.8;2.8 Socio-Cultural Aspects of Arsenicosis in Bangladesh;96
10.9;2.9 Conclusions;97
10.10;References;97
11;3 Arsenic and Fluorescent Humic Substances in the Ground Water of Bangladesh: A Public Health Risk;102
11.1;3.1 Introduction;102
11.2;3.2 Materials and Methods;103
11.2.1;3.2.1 Geologic and Demographic Overview;103
11.2.2;3.2.2 Sampling;105
11.2.3;3.2.3 Analysis;105
11.3;3.3 Results and Discussion;106
11.3.1;3.3.1 Groundwater Quality;106
11.3.2;3.3.2 Arsenic Poisoning in Ground Water;107
11.3.3;3.3.3 Arsenic in Rice and Vegetables;111
11.3.4;3.3.4 Fluorescence Properties of DOC;114
11.3.5;3.3.5 Molecular Characteristics of Humic Substances;117
11.3.6;3.3.6 Health Risks;117
11.4;3.4 Conclusions;119
11.5;References;120
12;4 Arsenic Risk Assessment;124
12.1;4.1 Introduction;124
12.2;4.2 Arsenic Chemistry;126
12.3;4.3 Arsenic Occurrence and Exposure;126
12.4;4.4 Hazard Identification;127
12.4.1;4.4.1 Arsenite and Arsenate;127
12.4.1.1;4.4.1.1 Skin Lesions;127
12.4.1.2;4.4.1.2 Cancer Effects;128
12.4.1.3;4.4.1.3 Diabetes;129
12.4.1.4;4.4.1.4 Cardiovascular Effects;129
12.4.1.5;4.4.1.5 Neurological Effects;130
12.4.1.6;4.4.1.6 Pulmonary Effects;130
12.4.1.7;4.4.1.7 Kidney Effects;131
12.4.1.8;4.4.1.8 Immune Effects;131
12.4.1.9;4.4.1.9 Other Effects;131
12.4.1.10;4.4.1.10 Developmental and Reproduction Effects;131
12.4.2;4.4.2 Hazard Identification—DMA and MMA;132
12.4.3;4.4.3 Hazard Identification—Arsine;132
12.5;4.5 Arsenic Metabolism, Mode of Action, and Physiologically Based Pharmacokinetic Modeling;132
12.6;4.6 Potential Sources of Susceptibility;135
12.7;4.7 Dose–Response Approaches;137
12.8;4.8 Risk Characterization;137
12.8.1;4.8.1 Reference Values and Regulatory Standards for Arsenical Compounds;137
12.8.1.1;4.8.1.1 US EPA;137
12.8.1.1.1;4.8.1.1.1 Inorganic Arsenic;137
12.8.1.1.2;4.8.1.1.2 Organoarsenicals;138
12.8.1.1.3;4.8.1.1.3 Arsine;138
12.8.1.2;4.8.1.2 ATSDR;138
12.8.1.2.1;4.8.1.2.1 Inorganic Arsenic;138
12.8.1.2.2;4.8.1.2.2 Organoarsenicals;139
12.8.1.3;4.8.1.3 RIVM National Institute for Public Health and the Environment;139
12.8.1.4;4.8.1.4 Other Standards, Regulations, and Guidelines;139
12.8.1.5;4.8.1.5 World Health Organization (WHO);139
12.8.1.6;4.8.1.6 California Environmental Protection Agency;139
12.8.1.7;Disclaimer;140
12.9;References;140
13;5 Evaluation of Novel Modified Activated Alumina as Adsorbent for Arsenic Removal;150
13.1;5.1 Introduction;150
13.2;5.2 Materials and Methods;151
13.2.1;5.2.1 Preparation of Sol-Gel Activated Alumina;151
13.2.2;5.2.2 Surface Modifications of Sol-Gel Activated Alumina;151
13.2.2.1;5.2.2.1 Characterization of Adsorbent Materials;152
13.2.3;5.2.3 Batch Adsorption Experiments;152
13.2.3.1;5.2.3.1 Breakthrough Column Experiments;153
13.2.3.2;5.2.3.2 Adsorbent Regeneration;154
13.3;5.3 Results and Discussion;154
13.3.1;5.3.1 Adsorbents Properties;154
13.3.2;5.3.2 Arsenic Adsorption Equilibrium;156
13.3.2.1;5.3.2.1 Solution pH as a Function of Adsorption Time;156
13.3.2.2;5.3.2.2 As Adsorbent Amount as a Function of pH;157
13.3.2.3;5.3.2.3 Effect of Initial Concentration on As Removal Efficiency;158
13.3.2.4;5.3.2.4 Adsorption Equilibrium;159
13.3.3;5.3.3 Breakthrough Column Analysis;161
13.3.4;5.3.4 Adsorbent Regeneration;163
13.4;5.4 Conclusions;163
13.5;Acknowledgments;164
13.6;References;164
14;6 Health Effects Chronic Arsenic Toxicity;166
14.1;6.1 Introduction;166
14.2;6.2 Dermatological Manifestations;167
14.2.1;6.2.1 Hyperpigmentation;167
14.2.2;6.2.2 Hypopigmentation;168
14.2.3;6.2.3 Hyperkeratosis;170
14.2.4;6.2.4 Bowen’s Disease;172
14.3;6.3 Epidemiological Study of Dermatological Manifestations;173
14.3.1;6.3.1 Systemic Manifestations;175
14.3.2;6.3.2 Respiratory Disease;176
14.3.2.1;6.3.2.1 Epidemiological Study;177
14.3.2.2;6.3.2.2 Mortality Studies;180
14.3.3;6.3.3 Gastrointestinal Disease;180
14.3.4;6.3.4 Liver Disease;181
14.3.4.1;6.3.4.1 Experimental Model for Liver Fibrosis;182
14.3.5;6.3.5 Cardiovascular Disease;182
14.3.6;6.3.6 Diseases of the Nervous System;184
14.3.7;6.3.7 Hematological Effects;186
14.3.8;6.3.8 Diabetes;187
14.3.9;6.3.9 Eye Disease;189
14.3.9.1;6.3.9.1 Conjunctivitis;189
14.3.9.2;6.3.9.2 Pterygium;189
14.3.9.3;6.3.9.3 Cataract;189
14.3.10;6.3.10 Non-Pitting Edema of Limbs;190
14.3.11;6.3.11 Miscellaneous;190
14.3.11.1;6.3.11.1 Weakness;190
14.3.11.2;6.3.11.2 Erectile Dysfunction;190
14.3.11.3;6.3.11.3 Proteinuria;191
14.4;6.4 Pregnancy Outcome;191
14.5;6.5 Arsenicosis and Cancer;192
14.5.1;6.5.1 Skin Cancer;192
14.5.2;6.5.2 Urinary Bladder Cancer;193
14.5.3;6.5.3 Lung Cancer;193
14.5.4;6.5.4 Other Cancers;194
14.6;6.6 Diagnosis;194
14.6.1;6.6.1 Biomarkers with Special Focus on Diagnosis;196
14.7;6.7 Treatment;197
14.7.1;6.7.1 Ceasing Drinking of Arsenic-Contaminated Water;197
14.7.2;6.7.2 Specific Therapy;198
14.8;References;200
15;7 Changing Concept of Arsenic Toxicity with Development of Speciation Techniques;208
15.1;7.1 Introduction;208
15.2;7.2 Conclusions;226
15.3;References;226
16;8 Mechanism for Arsenic-Induced Toxic Effects;232
16.1;8.1 Introduction;232
16.2;8.2 Biological Consequences of Chronic Arsenic Exposure in Humans;233
16.3;8.3 Arsenic Metabolism;234
16.3.1;8.3.1 Biomethylation;234
16.4;8.4 Pathophysiology of Arsenic Toxicity;235
16.4.1;8.4.1 Cardiovascular Dysfunction;235
16.4.2;8.4.2 Neurological Disorders;236
16.4.3;8.4.3 Hepatic and Renal Toxicity;237
16.4.4;8.4.4 Testicular Toxicity;238
16.4.5;8.4.5 Arsenic Carcinogenicity;239
16.5;8.5 Mechanism for the Toxic Effects of Arsenic;240
16.5.1;8.5.1 Oxidative Stress;240
16.5.2;8.5.2 Signaling Mechanism;241
16.5.3;8.5.3 Role of Transcription Factor;242
16.6;8.6 Preventing Arsenic-Induced Toxic Effects by Antioxidants;243
16.6.1;8.6.1 Role of Taurine;244
16.6.1.1;8.6.1.1 Taurine in Prevention of Arsenic-Induced Cardiac Disorder;244
16.6.1.2;8.6.1.2 Taurine against As-Induced Hepatic and Testicular Apoptosis;244
16.6.1.3;8.6.1.3 Taurine against As-Induced Oxidative Cerebral and Renal Disorders;246
16.6.2;8.6.2 Role of N-Acetyl Cysteine;246
16.6.3;8.6.3 Role of Melatonin;246
16.6.4;8.6.4 Role of a-Lipoic Acid;247
16.6.5;8.6.5 Role of Silymarin and Quercetin;247
16.6.6;8.6.6 Herbal Antioxidant;248
16.7;8.7 Conclusions and Future Directions;249
16.8;References;250
17;9 Arsenic-Induced Mutagenesis and Carcinogenesis: A Possible Mechanism;262
17.1;9.1 Arsenic, a Potent Mutagen and Carcinogen;262
17.2;9.2 Epidemiological Perspectives of Arsenic-Induced Human Cancers;263
17.3;9.3 Arsenic-Associated Metabolism and Carcinogenesis in Animal Models;264
17.3.1;9.3.1 Arsenic Metabolism and Carcinogenesis;265
17.3.2;9.3.2 Arsenic Metabolism and Free Radical Influences;267
17.3.3;9.3.3 Arsenic May Influence Drug Metabolizing Enzymes;269
17.3.4;9.3.4 Gut Microflora Influences Arsenic Toxicity and Tumorigenesis/Carcinogenesis;270
17.3.5;9.3.5 Arsenic-Induced Carcinogenesis in Animal Models: Role of Signal Transduction;271
17.3.6;9.3.6 Arsenic Induces Cellular Transformation Signaling;271
17.3.7;9.3.7 Arsenic and Epigenetic Modification;273
17.3.8;9.3.8 Arsenic and Tumor/Heat Shock-Associated Proteins;274
17.3.9;9.3.9 Arsenic and Apoptotic Signaling via Transcription Regulation;275
17.4;9.4 Human Arsenic Carcinogenesis;280
17.4.1;9.4.1 Genetic/Epigenetic Changes in Arsenic-Associated Human Carcinogenesis;280
17.4.2;9.4.2 Arsenic Affects Cultured Human Cells and Environmentally Exposed Human Populations;282
17.4.3;9.4.3 Arsenic Induces Telomere Instability;283
17.4.4;9.4.4 Arsenic-Associated DNA Damage and Genome Dysfunction in Humans;284
17.4.5;9.4.5 Arsenic and Epigenetic DNA Modification;285
17.4.6;9.4.6 Arsenic-Associated Signal Transduction Processes and Human Carcinogenesis;287
17.5;9.5 Conclusions and Future Directions;293
17.6;Acknowledgments;294
17.7;References;294
18;10 Arsenic Through the Gastrointestinal Tract;310
18.1;10.1 General Aspects;310
18.2;10.2 Arsenic in Foods: Household Processing and Toxicological Risk;311
18.3;10.3 Role of the Gut in Arsenic Toxicity: Bioavailability and Intestinal Health;312
18.3.1;10.3.1 Gastrointestinal Health;315
18.4;10.4 Arsenic-Induced Metabolic/Immune Toxicity;318
18.5;10.5 Conclusions and Future Perspectives;320
18.6;References;321
19;11 Cutaneous Toxicology of Arsenic;330
19.1;11.1 Introduction;330
19.2;11.2 Epidemiology;331
19.3;11.3 Clinical Manifestations;332
19.4;11.4 Histopathology;333
19.5;11.5 Molecular Pathogenesis;333
19.5.1;11.5.1 Oxidative Stress;333
19.5.2;11.5.2 Genotoxicity;334
19.5.3;11.5.3 Disrupted Signal Transduction Pathways;334
19.5.4;11.5.4 Immune Dysfunction and Inflammatory Responses;336
19.6;11.6 Treatment;339
19.7;References;340
20;12 Arsenic-Induced Liver Injury;344
20.1;12.1 Introduction;344
20.2;12.2 Source of Exposure;345
20.3;12.3 Biotransformation and Elimination of Arsenic;346
20.4;12.4 History of Arsenic-Related Liver Diseases;347
20.5;12.5 Hepatoportal Sclerosis;348
20.6;12.6 Arsenic-Related Hepatic Fibrosis and Cirrhosis;349
20.7;12.7 Epidemiological Study to Assess Arsenic-Related Liver Dysfunction;350
20.8;12.8 Animal Studies for Understanding the Pathogenesis;351
20.9;12.9 Arsenic and Liver Cancer;358
20.10;References;359
21;13 Arsenic and Respiratory Disease;364
21.1;13.1 Introduction;364
21.1.1;13.1.1 Lung Development;365
21.2;13.2 Chronic Arsenic Exposure and Respiratory Health;365
21.2.1;13.2.1 Chronic Arsenic Exposure and Respiratory Symptoms;365
21.2.2;13.2.2 Chronic Arsenic Exposure and Lung Function;365
21.2.3;13.2.3 Chronic Arsenic Exposure and Immunosuppression;366
21.2.4;13.2.4 Chronic Arsenic Exposure and Non-Malignant Respiratory Disease;366
21.3;13.3 Early Life Arsenic Exposure and Lung Health;367
21.3.1;13.3.1 Early Life Arsenic Exposure, Birth Outcomes, and Growth;367
21.3.2;13.3.2 Early Life Arsenic Exposure and Immune Development;367
21.3.3;13.3.3 Early Life Arsenic Exposure and Non-Malignant Respiratory Disease in Children;368
21.3.4;13.3.4 Early Life Arsenic Exposure and Non-Malignant Respiratory Disease in Adults;369
21.4;13.4 Mechanistic Data on Arsenic Exposure and the Lung;370
21.4.1;13.4.1 Mechanistic Data on Early Life Arsenic Exposure;370
21.4.2;13.4.2 Mechanistic Data for Arsenic Exposure and Immune Function;370
21.4.3;13.4.3 Mechanistic Data for Arsenic Exposure and Lung Structure and Function;371
21.5;13.5 Conclusions;372
21.6;References;372
22;14 Arsenical Kidney Toxicity;378
22.1;14.1 Introduction;378
22.2;14.2 Clinical Manifestations of Arsenical Toxicity in Humans;379
22.2.1;14.2.1 Epidemiological Studies;379
22.2.2;14.2.2 Mechanisms of Arsenical Toxicity to Specific Renal Cell Populations;379
22.2.2.1;14.2.2.1 Renal Blood Vasculature;379
22.2.2.2;14.2.2.2 Proximal Tubules;380
22.3;14.3 Nephrotoxic Arsenical Compounds;380
22.3.1;14.3.1 Arsine;380
22.3.2;14.3.2 Arsenate;380
22.3.3;14.3.3 Arsenite;381
22.4;14.4 Mechanisms of Arsenical Toxicity;381
22.4.1;14.4.1 Mitochondrial Effects;381
22.4.1.1;14.4.1.1 Mitochondrial Respiratory Function;381
22.4.1.2;14.4.1.2 Heme Biosynthetic Pathway;381
22.4.1.3;14.4.1.3 Arsenic and Renal Cancer;382
22.4.1.4;14.4.1.4 Membrane Transport Systems;382
22.4.1.5;14.4.1.5 Altered Cellular Signaling Pathways;382
22.5;14.5 Biomarkers of Nephrotoxicity;383
22.5.1;14.5.1 Omic Biomarkers;383
22.5.2;14.5.2 Altered Gene Expression Patterns (Genomics);383
22.5.3;14.5.3 Altered Protein Synthesis Patterns (Proteomics);384
22.5.4;14.5.4 Metabolomics;384
22.5.5;14.5.5 Arsenic-Induced Posttranslational Alterations of Proteins;385
22.5.6;14.5.6 Altered Heme Biosynthesis/Porphyrinuria Patterns;385
22.5.7;14.5.7 Proteinuria Patterns;385
22.6;14.6 Arsenical Interactions with Other Nephrotoxic Elements;385
22.6.1;14.6.1 Lead;385
22.6.2;14.6.2 Cadmium;386
22.6.3;14.6.3 Gallium;386
22.6.4;14.6.4 Indium;386
22.7;14.7 Summary and Future Research Needs;386
22.8;References;386
23;15 Arsenic-Induced Developmental Neurotoxicity;392
23.1;15.1 Introduction;392
23.2;15.2 Arsenic Exposure Impairs Intellectual Function in Children;393
23.3;15.3 Developmental Neurobehavioral Toxicity in Animals;396
23.4;15.4 Arsenic Distribution After Exposure in Early Life;397
23.5;15.5 Mechanism of Developmental Neurotoxicity;398
23.5.1;15.5.1 Effects of Arsenic on Neurotransmitter Systems;398
23.5.2;15.5.2 Arsenic and Neurite Growth, Astrocyte, and Myelin;399
23.5.3;15.5.3 Arsenic and Neuron Apoptosis;401
23.5.4;15.5.4 Arsenic and Methylation;402
23.5.5;15.5.5 Arsenic and Nitric Oxide;403
23.5.6;15.5.6 Arsenic and Gene Expression;403
23.6;15.6 Neuroprotective Agents Against Arsenic Toxicity;405
23.7;15.7 Conclusions;406
23.8;References;409
24;16 Developmental Arsenic Exposure Impacts Fetal Programming of the Nervous System;416
24.1;16.1 Introduction;416
24.2;16.2 Accumulation of Arsenic in Fetal Brain Tissue;417
24.3;16.3 Effect of Arsenic on the Development of the Nervous System;418
24.4;16.4 Effect of Arsenic on Neurobehavior;420
24.5;16.5 Mechanisms for the Effect of Arsenic on the Nervous System During Development;424
24.5.1;16.5.1 Induction of Oxidative Stress;424
24.5.2;16.5.2 Induction of Apoptosis;425
24.5.3;16.5.3 Effect of Arsenic on the Cell Cycle;426
24.5.4;16.5.4 Effect on Central Neurotransmitters/Neuroendocrine;426
24.5.5;16.5.5 Other Mechanisms;427
24.6;16.6 Conclusions and Future Directions;428
24.7;References;428
25;17 Health Effects of Prenatal and Early-Life Exposure to Arsenic;434
25.1;17.1 Introduction;434
25.2;17.2 Adverse Health Effects Associated with Chronic and Early-Life Arsenic Exposure;435
25.2.1;17.2.1 Health Effects Associated with Chronic Exposure to iAs;435
25.2.2;17.2.2 Health Effects Associated with iAs Exposure during Gestation and Infancy;436
25.2.3;17.2.3 Health Effects of iAs Exposure Observed in Childhood;437
25.2.4;17.2.4 Delayed Health Effects Associated with Chronic and Prenatal Arsenic Exposure;438
25.3;17.3 Mechanisms Implicated in Disease Development Associated with Prenatal Exposure;441
25.3.1;17.3.1 Epigenetic Reprogramming as a Potential Key Event in Latent Disease Development;441
25.3.1.1;17.3.1.1 Epigenetic and Genomic Alterations in Experimental Animals;443
25.3.1.2;17.3.1.2 Epigenetic and Genomic Alterations in Human Populations;445
25.3.2;17.3.2 Role of Cancer Stem Cells;447
25.3.3;17.3.3 Immunomodulatory Effects;449
25.4;17.4 Conclusions and Future Directions;450
25.5;References;450
26;18 Arsenic, Kidney, and Urinary Bladder Disorders;458
26.1;18.1 Introduction;458
26.2;18.2 Arsenic and Renal Disease;459
26.2.1;18.2.1 Studies in Animals;459
26.2.2;18.2.2 Epidemiological Studies in Humans;460
26.2.3;18.2.3 Early Biomarkers of Arsenic Exposure and Nephrotoxicity;462
26.2.4;18.2.4 Physiopathology;463
26.2.5;18.2.5 Clinical Manifestations of Arsenic-induced Renal Disease;465
26.3;18.3 Arsenic and Bladder Disease;465
26.4;References;467
27;19 Developmental Arsenic Exposure: Behavioral Dysfunctions and Neurochemical Perturbations;472
27.1;19.1 Introduction;472
27.2;19.2 Toxicity;473
27.3;19.3 Developmental Toxicity;473
27.3.1;19.3.1 Effects on the Nervous System;474
27.3.1.1;19.3.1.1 Neurochemical Effects;474
27.3.1.1.1;19.3.1.1.1 Neurotransmitter Systems;474
27.3.1.1.2;19.3.1.1.2 Oxidative Stress;475
27.3.1.1.3;19.3.1.1.3 Neurite Outgrowth;476
27.3.2;19.3.2 Behavioral Effects;476
27.4;19.4 Conclusions;478
27.5;References;480
28;20 Arsenic and the Cardiovascular System;488
28.1;20.1 Introduction;488
28.2;20.2 Cardiovascular System;490
28.3;20.3 Arsenic Effects on Blood;491
28.3.1;20.3.1 Erythrocytes;491
28.3.2;20.3.2 Leukocytes;493
28.3.3;20.3.3 Methyltransferases;496
28.4;20.4 Arsenic Effects on the Vascular System;497
28.4.1;20.4.1 Clinical Studies;497
28.4.2;20.4.2 Atherosclerosis;499
28.4.3;20.4.3 Genetic Polymorphisms;499
28.4.4;20.4.4 Endothelial Cells;501
28.4.5;20.4.5 Smooth Muscle Cells;502
28.5;20.5 Arsenic Effects on the Heart;503
28.5.1;20.5.1 QT Prolongation;503
28.5.2;20.5.2 Ischemic Heart Disease;504
28.5.3;20.5.3 Ion Channels;505
28.5.4;20.5.4 Cellular Signaling;507
28.5.5;20.5.5 Chelation Therapy;510
28.6;20.6 Human Pluripotent Stem Cells: Understanding Arsenic Toxicity;510
28.7;20.7 Conclusions;512
28.8;References;512
29;21 Immunotoxic Effects of Arsenic Exposure;522
29.1;21.1 Introduction;523
29.2;21.2 Influence of Nutritional Factors;525
29.3;21.3 Effects on Blood Leukocytes;525
29.4;21.4 Interruption of Energy Production;525
29.5;21.5 Effects on ROS Production;526
29.6;21.6 Genotoxic and Carcinogenic Potentials;526
29.7;21.7 Hematological Effects on Experimental Animals;527
29.8;21.8 Effect on Heme Synthesis;528
29.9;21.9 Hepatic Effects and Lipid Peroxidation;528
29.10;21.10 Effects on Immune Responses in Fish;529
29.10.1;21.10.1 Innate Immune Response;529
29.10.2;21.10.2 Humoral Immune Response;529
29.11;21.11 Effects on Immune Responses in Laboratory Animals;530
29.11.1;21.11.1 Humoral Immune Response;530
29.11.2;21.11.2 Cell-Mediated Immune Response;530
29.12;21.12 Effects of Arsenic in Drinking Water on Human Health;531
29.13;21.13 Immunotoxic Effects of Organic Arsenicals in Foods;532
29.14;21.14 Medicinal Use of Arsenic and Its Mechanism of Action;533
29.15;21.15 Effects of Arsenic Compounds on Human Cells in Culture;533
29.15.1;21.15.1 Effects on Growth-Promoting Cytokines and Growth Factors;534
29.15.2;21.15.2 Effects on Human T-Cell Functional Responses;535
29.16;21.16 Immunotoxic Effects on Murine and Human Monocytes/Macrophages;535
29.16.1;21.16.1 Effects on Monocyte/Macrophage Functional Responses;537
29.16.2;21.16.2 Impairment of Macrophage-Functional Genes;537
29.17;21.17 Immunotoxic Effects on Murine Mononuclear Cells;538
29.18;21.18 Decreased Cytokine Production by Human T Cells;538
29.19;21.19 Effects of In Utero Exposure on Infant Immune System;539
29.20;21.20 Gender-Related Immunotoxic Effects in Human;539
29.21;21.21 Effects of Chronic Exposure on Immune Response;540
29.21.1;21.21.1 Effects of Chronic Exposure on Mice and Human Lungs;540
29.21.2;21.21.2 Effects of Chronic Exposure on Humoral Immune Response in Humans;541
29.22;21.22 Association with Respiratory Complications and Impaired Immune Responses;541
29.23;21.23 Effects of Chronic Exposure on Serum Complement Function;542
29.24;21.24 Conclusions;542
29.25;References;543
30;22 Arsenic and Developmental Toxicity and Reproductive Disorders;550
30.1;22.1 Introduction;550
30.2;22.2 Developmental Toxicity;552
30.2.1;22.2.1 Neural Tube Defects;552
30.2.1.1;22.2.1.1 Animal Models;552
30.2.1.1.1;22.2.1.1.1 Human Studies;553
30.2.1.1.2;22.2.1.1.2 Other Birth Defects;553
30.3;22.3 Reproductive Toxicity;554
30.3.1;22.3.1 Infant Mortality;554
30.3.2;22.3.2 Birth Weight;554
30.4;22.4 Early-Life Exposures and Delayed Health Effects;555
30.5;22.5 Reproductive Disorders;556
30.5.1;22.5.1 Male Infertility;556
30.5.1.1;22.5.1.1 Animal Studies;556
30.5.1.2;22.5.1.2 Human Studies;556
30.6;22.6 Conclusions;557
30.7;References;557
31;23 Arsenic and Cancer;562
31.1;23.1 Arsenic and Arsenic-Containing Compounds;562
31.2;23.2 Sources of Arsenic and Potential for Human Exposure;564
31.2.1;23.2.1 Arsenic and Drinking Water Contamination;564
31.2.2;23.2.2 Arsenic and Food Contamination;564
31.2.3;23.2.3 Arsenic and Soil Contamination;565
31.2.4;23.2.4 Arsenic and Air Pollution;565
31.2.5;23.2.5 Arsenic Exposure from Medication;566
31.2.6;23.2.6 Occupational Exposure to Arsenic;566
31.3;23.3 Molecular Mechanisms of Arsenic-Induced Carcinogenesis;567
31.3.1;23.3.1 Arsenic Perturbation of Keratin Expression;568
31.3.2;23.3.2 Arsenic-Induced Genotoxicity;569
31.3.3;23.3.3 Arsenic-Induced Aberration of Gene Expression;569
31.3.4;23.3.4 Arsenic Dysregulation of Cellular Immune Function;569
31.3.5;23.3.5 Arsenic Distortion of Protein Structure;570
31.3.6;23.3.6 Arsenic Induction of Cell Proliferation;570
31.3.7;23.3.7 Arsenic Dysregulation of Epigenetic Mechanisms;570
31.3.8;23.3.8 Arsenic Cocarcinogenicity;570
31.3.9;23.3.9 Arsenic Interference with Signal Transduction;571
31.3.10;23.3.10 Arsenic Induction of Reactive Oxygen Species;571
31.4;23.4 Health Effects Associated with Arsenic Exposure;572
31.4.1;23.4.1 Arsenic and Keratosis;572
31.4.2;23.4.2 Arsenic and Skin Cancer;574
31.4.3;23.4.3 Arsenic and Liver Cancer;575
31.4.4;23.4.4 Arsenic and Kidney Cancer;575
31.4.5;23.4.5 Arsenic and Urinary Bladder Cancer;576
31.4.6;23.4.6 Arsenic and Lung Cancer;576
31.4.7;23.4.7 Arsenic and Gastrointestinal Cancer;577
31.4.8;23.4.8 Arsenic and Brain Cancer;577
31.5;23.5 Conclusions;578
31.6;Acknowledgments;578
31.7;References;578
32;24 The Association between Chronic Arsenic Exposure and Type 2 Diabetes: A Meta-Analysis;586
32.1;24.1 Introduction;586
32.2;24.2 Methods and Materials;588
32.2.1;24.2.1 Literature Search;588
32.2.2;24.2.2 Selection of Studies;588
32.2.2.1;24.2.2.1 Quality of the Studies;588
32.2.2.2;24.2.2.2 Statistical Analysis;589
32.3;24.3 Results;589
32.3.1;24.3.1 Literature Search;589
32.3.2;24.3.2 Quality Scoring;590
32.3.3;24.3.3 Sources of Heterogeneity;590
32.3.4;24.3.4 Meta-Regression and Sensitivity Analysis;596
32.3.5;24.3.5 Influence Analysis;596
32.3.6;24.3.6 Publication Bias;596
32.3.7;24.3.7 Dose–Response;597
32.4;24.4 Discussion;597
32.5;References;599
33;25 Arsenic Biosensors: Challenges and Opportunities for High-Throughput Detection;604
33.1;25.1 Arsenic: The Toxic Metalloid;604
33.2;25.2 Arsenic Biosensors;605
33.2.1;25.2.1 Evolution of a Natural Self-Defense Mechanism—the ars Operon;606
33.2.2;25.2.2 Recombinant Escherichia coli—the Favored Biorecognition Element;606
33.3;25.3 Nanosensor Platforms—Towards High-Throughput Detection;610
33.4;25.4 Conclusions and Future Directions;614
33.5;References;615
34;26 Medical Countermeasures—Chelation Therapy;618
34.1;26.1 Introduction;618
34.2;26.2 Clinical Aspects of Arsenic;619
34.3;26.3 Diagnosis;620
34.4;26.4 Chelation Therapy;621
34.4.1;26.4.1 Concept;621
34.4.2;26.4.2 Chemistry;622
34.4.3;26.4.3 Chemical Considerations;623
34.4.3.1;26.4.3.1 Thermodynamics of Metal Chelation;623
34.4.3.2;26.4.3.2 Kinetic Considerations in Metal Chelation;624
34.4.3.3;26.4.3.3 In Vivo Efficacy of Chelating Agents;624
34.4.4;26.4.4 Toxicokinetics of Chelation;625
34.5;26.5 Chelators in Clinical Use;627
34.5.1;26.5.1 Chelating Agents for Arsenic Poisoning;627
34.5.1.1;26.5.1.1 Dimercaprol (BAL);627
34.5.1.1.1;26.5.1.1.1 Chemistry, Pharmacokinetics, and Pharmacodynamics;627
34.5.1.1.2;26.5.1.1.2 Efficacy and Experimental Studies;627
34.5.1.1.3;26.5.1.1.3 Mechanism of Action;627
34.5.1.1.4;26.5.1.1.4 Human Cases;628
34.5.1.1.5;26.5.1.1.5 Drawbacks;629
34.5.1.2;26.5.1.2 D-Penicillamine (D-PA);630
34.5.1.2.1;26.5.1.2.1 Chemistry, Pharmacokinetics, and Pharmacodynamics;630
34.5.1.2.2;26.5.1.2.2 Efficacy and Experimental Studies;630
34.5.1.2.3;26.5.1.2.3 Mechanism of Action;630
34.5.1.2.4;26.5.1.2.4 Human Studies;630
34.5.1.2.5;26.5.1.2.5 Drawbacks;630
34.5.1.3;26.5.1.3 Meso-2,3-Dimercaptosuccinic Acid (Succimer, DMSA);631
34.5.1.3.1;26.5.1.3.1 Chemistry, Pharmacokinetics, and Pharmacodynamics;631
34.5.1.3.2;26.5.1.3.2 Efficacy and Experimental Studies;631
34.5.1.3.3;26.5.1.3.3 Mechanism of Action;631
34.5.1.3.4;26.5.1.3.4 Human Studies;632
34.5.1.3.5;26.5.1.3.5 Drawbacks;632
34.5.1.4;26.5.1.4 2,3-Dimercaptopropane-1-Sulfonic Acid;633
34.5.1.4.1;26.5.1.4.1 Chemistry, Pharmacokinetics, and Pharmacodynamics;633
34.5.1.4.2;26.5.1.4.2 Efficacy and Experimental Studies;633
34.5.1.4.3;26.5.1.4.3 Mechanism of Action;633
34.5.1.4.4;26.5.1.4.4 Human Studies;633
34.5.1.4.5;26.5.1.4.5 Drawbacks;634
34.6;26.6 Analogues of DMSA as Potential New Arsenic Chelators;634
34.6.1;26.6.1 Monoisoamyl DMSA (MiADMSA);634
34.6.1.1;26.6.1.1 Chemistry, Pharmacokinetics, and Pharmacodynamics;634
34.6.1.2;26.6.1.2 Efficacy and Experimental Studies;635
34.6.1.3;26.6.1.3 Mechanism of Action;636
34.6.1.4;26.6.1.4 Drawbacks;636
34.6.2;26.6.2 Monomethyl DMSA (MmDMSA) and Monocyclohexyl DMSA (MchDMSA);636
34.7;26.7 Role of Antioxidants in Preventing Arsenic Toxicity;637
34.7.1;26.7.1 Alpha-Lipoic Acid;638
34.7.2;26.7.2 N-Acetylcysteine;638
34.7.3;26.7.3 Vitamins E and C;639
34.7.4;26.7.4 ß-Carotene;640
34.7.5;26.7.5 Taurine;640
34.7.6;26.7.6 Melatonin;640
34.7.7;26.7.7 Curcumin;641
34.7.8;26.7.8 Essential Metals;641
34.7.8.1;26.7.8.1 Zinc;641
34.7.8.2;26.7.8.2 Selenium;642
34.7.9;26.7.9 Herbal Extracts;642
34.8;26.8 Newer Strategies;643
34.8.1;26.8.1 Combination Therapy;643
34.8.2;26.8.2 Nanoparticle Carriers to Combat Arsenic Toxicity;644
34.9;26.9 Concluding Remarks and Future Directions;647
34.10;References;647
35;27 Biochemical and Molecular Basis of Arsenic Toxicity and Tolerance in Microbes and Plants;656
35.1;27.1 Introduction;656
35.1.1;27.1.1 Arsenic: A Threatening Environmental Issue;656
35.1.2;27.1.2 Worldwide Occurrence of Arsenic;657
35.1.3;27.1.3 Arsenic Speciation and Mobilization;658
35.1.4;27.1.4 Arsenic Epidemiology;659
35.2;27.2 Arsenic Toxicity and Tolerance in Microbes;660
35.2.1;27.2.1 Arsenic Uptake Pathways;661
35.2.2;27.2.2 Extracellular Immobilization of Arsenic;662
35.2.3;27.2.3 Arsenic Chelation;662
35.2.4;27.2.4 Arsenate Reduction;662
35.2.4.1;27.2.4.1 Mechanism of Arsenic Detoxification;662
35.2.4.2;27.2.4.2 Arsenate Respiration or Dissimilatory As(V) Reduction;664
35.2.5;27.2.5 Efflux of As(III) from the Cell;665
35.2.6;27.2.6 Oxidation of As(III);665
35.2.6.1;27.2.6.1 Mechanism of As(III) Oxidation;666
35.2.7;27.2.7 Arsenic Biomethylation;668
35.2.7.1;27.2.7.1 Methylation Pathway;669
35.2.8;27.2.8 Morphological, Physiological, and Biochemical Responses;670
35.3;27.3 Arsenic Toxicity and Tolerance in planta;670
35.3.1;27.3.1 Arsenic Uptake and Efflux;671
35.3.1.1;27.3.1.1 Arsenate Uptake;672
35.3.1.2;27.3.1.2 Arsenite Uptake;673
35.3.1.3;27.3.1.3 Uptake of Methylated Arsenic;673
35.3.1.4;27.3.1.4 Long-Distance Transport;674
35.3.2;27.3.2 Arsenic Toxicity to Plants;674
35.3.2.1;27.3.2.1 Impact on Morphology, Growth, and Productivity;674
35.3.2.2;27.3.2.2 Physiological and Biochemical Responses;675
35.3.2.3;27.3.2.3 Proteomic Responses of Plants to As Stress;675
35.3.3;27.3.3 Mechanism of As Toxicity;676
35.3.3.1;27.3.3.1 Phosphate Replacement;677
35.3.3.2;27.3.3.2 Binding Thiol Groups;678
35.4;27.4 Mechanisms of As Tolerance and Detoxification;680
35.4.1;27.4.1 Arsenate Reduction;680
35.4.2;27.4.2 Complexation and Sequestration of As;681
35.4.3;27.4.3 Antioxidative Defense System;683
35.4.4;27.4.4 Osmolyte Accumulation;684
35.4.5;27.4.5 Mycorrhization in Crop Plants: the Prospects of Arbuscular Mycorrhizae Symbiosis in Regulation of Plant Defense Resp ...;685
35.5;27.5 As Hyperaccumulation and Phytoextraction;686
35.5.1;27.5.1 Mechanisms of As Hyperaccumulation;686
35.6;27.6 Summary Points;687
35.7;Acknowledgments;688
35.8;References;688
36;28 Arsenic Contents and Its Biotransformation in the Marine Environment;704
36.1;28.1 Introduction;704
36.2;28.2 Arsenic Concentration in Sea Water;705
36.3;28.3 Arsenic Concentration in Marine Sediments;708
36.4;28.4 Arsenic Speciation in Marine Ecosystems;710
36.5;28.5 Arsenic Cycle in the Marine Environment;712
36.6;28.6 Role of Marine Biological Systems in Arsenic Biotransformation;715
36.6.1;28.6.1 Phytoplankton;715
36.6.2;28.6.2 Marine Bacteria;716
36.6.3;28.6.3 Algae;718
36.6.4;28.6.4 Marine Animals;719
36.7;28.7 Arsenic in Seafood and Its Toxicity;720
36.8;28.8 Future Directions;723
36.9;References;723
37;Index;730

Leseproben

Preface
Swaran J.S. Flora I have been a chemical toxicologist for nearly 35 years. In this time, I have studied and evaluated the toxicities of toxic metals and the health effects produced by human exposure to metals. Arsenic, a naturally occurring metalloid, is ubiquitously present in the environment. Arsenic is ranked first among toxicants posing a significant potential threat to human health based on known or suspected toxicity. This naturally occurring metalloid is a known poison, a co-carcinogen, and in lower concentrations has been shown to cause damage to almost all major organs including liver, lungs, bladder and brain. Currently, the permitted concentration of arsenic in water is 10 µg/L (10 ppb). Yet, an estimated 100 million people worldwide are exposed to excessive amounts of arsenic via drinking water (in the ppm, not ppb, range). Many of these individuals obtain drinking water from unregulated sources (wells) or live in regions where arsenic levels are high, such as Bangladesh. Arsenic leaches from rock formations into water sources as the water table recedes, and hence exposure to high amounts of arsenic will continue to persist whilst the demand for clean water increases. This phenomenon particularly affects the Western region of the United States, where it is estimated that certain areas contain up to 3100 µg/L arsenic (31 ppm) in drinking water, on par with levels reported in Taiwan, China, Bangladesh and India. Although the largest number of people affected worldwide by the arsenic contamination of drinking water are in Bangladesh, the problem is not unique to that area. As early as 1960, scientists reported the link between various forms of cancer and arsenic in drinking water in Taiwan. Communities in North and South America, Europe, Asia and Australia also face the problem of arsenic-contaminated drinking water. The problem of arsenic-contaminated groundwater is found in communities throughout Canada and western USA that use groundwater as their source of drinking water. It is now almost certain that arsenic contamination is a worldwide problem; however, some of the most affected regions lie in the flood plains of the great rivers of Bangladesh, Nepal, and West Bengal, India. In Bangladesh alone, seventy million people are impacted. Problems associated with drinking groundwater were first noticed in Bangladesh by healthcare workers in the early 1990s. While the World Health Organization (WHO) and the Environmental Protection Agency (EPA) regulate water sources of arsenic, lack of strict regulations on food, beverages, and air quality can lead to increased arsenic exposure. Ingestion of arsenic activates metabolic pathways for excretion, resulting in a number of metabolites, some of which are more potent and toxic than the originally ingested inorganic form of arsenic. Inorganic arsenic exposure of humans, by the inhalation route, has been shown to be strongly associated with lung cancer, while ingestion of inorganic arsenic by humans has been linked to a form of skin cancer and also to bladder, liver, and lung cancer. The EPA has classified inorganic arsenic as a human carcinogen. This explosion of information in the recent years reflects the vast increase in number of researchers studying about the mechanisms of action of arsenic. The specific knowledge of the chemistry, biochemistry, toxicology, and epidemiology of arsenic is far greater than that for any other environmentally-occurring chemical carcinogen. This book really began over 20 years ago, when I was confronted with the first of scores of instances in Uttar Pradesh, Maharashtra, West Bengal and Bihar in India, where individuals exposed to arsenic subsequently developed symptoms and effects that could notably be explained by the known toxicological effects. In some instances the exposures led to effects far in excess of what would be expected. In others, effects were noted following exposures to extremely low levels of arsenic; in even more instances the body organs targeted were not those known to be impacted by arsenic. I carried out number of studies during these years; a few of them with my colleagues in West Bengal. These studies led to one serious concern: that we do not have a safe, specific and effective chelating drugs in this part of the world, and those drugs available in the developed countries are largely ineffective against arsenic toxicity. As time progressed, I began to think that the task was too big and a solution remained elusive. The breakthrough came when I got a reprint from Prof. M.M. Jones, Vanderbilt University in which his group synthesized and evaluated the efficacy of number of di- and monoesters of meso 2,3-dimercaptosuccinic acid (DMSA) with limited success against cadmium intoxication. There was a small but an interesting note on the top of the reprints written in red ink, where he asked me to try these esters against arsenic. This led me to my interest in arsenic poisoning and in particular searching for a new chelating agent. A review of the literature and our research group’s own studies highlighted the shortcomings with DMSA, DMPS and BAL, and it was then hypothesized that monoesters of DMSA might be a better option to treat cases of arsenicosis. I have attempted to bring together as comprehensive a group of scientists as possible in assembling this book. Whilst at first glance, the literature on arsenic toxicology seems exhaustive and systematic, this is not the case. There is no comprehensive and in-depth analysis of its effects on major organs, preventive and therapeutic measures; additionally, there are a few new topics where not much work has been undertaken but could be of potential future interest. This book thus promises to provide a comprehensive coverage of arsenic and its toxic effects, including its toxicokinetics, mode(s) of action, effects on all major organs and medical countermeasures. To my knowledge, this book perhaps is the first in-depth analysis of data on toxicology, risk assessment, and management. Included in these 28 chapters are detailed reviews of the many important mechanistic aspects of arsenic. Chapters 1 and 2 provide an orientation and introduction to the subject of arsenic. The focus of these chapters is to provide an overview of various critical factors affecting arsenic chemistry, the natural and anthropogenic sources of exposure. The focus of Chapters 3 and 4 are risk assessment following arsenic exposure while Chapter 5 provides data for the removal of arsenic using activated alumina (AA) and modified AA adsorbents. Chapters 5 and 6 provide information on the general health effects of arsenic and the role of arsenic metabolites in the toxic manifestation, respectively. Chapters 7–9 focus on various proposed modes of actions for arsenic, exposure pathways and toxicokinetics, various alterations in mediating genotoxic effects such as altered DNA repair, signal transduction, cellular proliferation, and altered DNA methylation. One of the major mechanisms of arsenic-induced toxic manifestation is oxidative stress. These chapters provide in-depth information regarding alterations at the biochemical level, detailed mechanisms of toxicity and oxidative injury, and the links between arsenic, oxidative stress and cancer. Chapter 10 discusses the gastrointestinal tract as one of the target organs of arsenic and a factor affecting its toxicity and the resultant risk assessments required. The authors suggest that arsenic species with higher toxicity degree than those ingested may appear in the intestinal lumen as a result of interactions with food components and from metabolism by enterocytes and micro biota. Also, the biotransformation may modulate arsenic intestinal absorption and therefore adverse effects. Although arsenic impacts on the physiological cellular processes in numerous organ systems, the outcomes of its toxicity are usually first seen in the skin. The major focus of Chapter 11 is on skin manifestations from acute toxicity such as flushing, erythema, facial edema, acrodynia, urticarial, alopecia, loss of nails, and Mees lines visible on nails. The liver is the target organ of arsenic and many important various metabolizing reactions take place in liver, rendering it the most susceptible organ to any xenobiotic. Exposure to arsenic leads to various hepatic disorders, which has been discussed in Chapter 12. Arsenic, the only environmental toxicant has been linked to both malignant and non-malignant respiratory disease following ingestion, rather than inhalation, making arsenic a unique toxicant to the respiratory system. Chapter 13 suggests that chronic exposure to arsenic has been associated with the development of respiratory symptoms, impaired lung function and chronic lung disease. Chapter 14 provides an overview of information that arsenic disturbs various vital renal functions such as the excretion of nitrogenous waste products and maintenance of electrolyte balance, which leads to immediate effects on circulating blood and hence whole body. Chapter 15, 16, 17, and 19 make a strong argument for the potential role of arsenic in disrupting the normal functions of the central nervous system, thereby causing impairment of learning, concentration and short term memory. It also alters the release of various neurotransmitters. Since the brain is the most vital organ, it’s important to fully understand the effect of arsenic intoxication and associated neuropathologies, which are discussed here. Arsenic accumulates in the urinary bladder epithelium, causing activation of specific signaling pathways, leading to increased cell proliferation and increased...