Arsenic

This book illustrates the chemistry, toxicology, and health effects of arsenic using novel modeling techniques, case studies, experimental data, and future perspectives.

• Covers exposure sources, health risks, and mechanisms of one of the most toxic minerals in the world
• Helps readers understand potential health effects of arsenic, using population studies, mammalian and invertebrate models, and pharmacokinetic and toxicokinetic models
• Discusses outcomes, epidemiology, real-life examples, and modes of action for arsenic-induced diseases, like lung cancer, diabetes, cardiovascular and pulmonary diseases, and immunotoxicity
• Acts as a reference for toxicologists, environmental chemists, and risk assessors and includes up-to-date, novel modeling techniques for scientists
• Includes future perspectives on special topics, like extrapolation from experimental models to human exposures, biomarkers for phenotypic anchoring, and pathology of chronic exposure

Contributors ix

Preface xiii

Part I Fundamentals of Arsenic Exposure and Metabolism 1

1 History of Arsenic as a Poison and a Medicinal Agent 3
Michael F. Hughes

2 Geogenic and Anthropogenic Arsenic Hazard in Groundwaters and Soils: Distribution, Nature, Origin, and Human Exposure Routes 23
David A. Polya and Michael Lawson

3 Remediation of Arsenic in Drinking Water 61
Cathleen J. Webb and Arden D. Davis

4 The Chemistry and Metabolism of Arsenic 81
David J. Thomas

Part II Epidemiology and Disease Manifestations of Arsenic Exposure 111

5 Human Population Studies and Nutritional Intervention 113
Yu Chen and Fen Wu

6 Skin Manifestations of Chronic Arsenicosis 127
Nilendu Sarma

7 Lung Cancer and Other Pulmonary Diseases 137
Cara L. Sherwood and R. Clark Lantz

8 Bladder Cancer and Arsenic 163
Matthew K. Medeiros and A. Jay Gandolfi

9 Neurological Effects of Arsenic Exposure 193
Dominic B. Fee

10 Diabetes Mellitus 221
Miroslav Styblo and Christelle Douillet

11 Hepatotoxicity 249
Gavin E. Arteel

12 Genetic Epidemiology of Susceptibility to Arsenic‐Induced Diseases 267
Mayukh Banerjee and Ashok K. Giri

Part III Mechanisms of Toxicity 289

13 Arsenic Interaction with Zinc Finger Motifs 291
Laurie G. Hudson, Karen L. Cooper, Susan R. Atlas, Brenee S. King and Ke Jian Liu

14 Role in Chemotherapy 315
Koren K. Mann and Maryse Lemaire

15 Genotoxicity 347
Ana Maria Salazar and Patricia Ostrosky‐Wegman

16 Arsenic and Signal Transduction 369
Ingrid L. Druwe and Richard R. Vaillancourt

17 Stem Cell Targeting and Alteration by Arsenic 397
Yuanyuan Xu, Erik J. Tokar and Michael P. Waalkes

18 Epigenetics and Arsenic Toxicity 421
Somnath Paul and Pritha Bhattacharjee

Part IV Models for Arsenic Toxicology and Risk Assessment 439

19 Cancer Induced by Exposure to Arsenicals in Animals 441
Erik J. Tokar, Yuanyuan Xu and Michael P. Waalkes

20 Arsenic‐Induced Cardiovascular Disease 453
Aaron Barchowsky and J. Christopher States

21 Invertebrate Models in Arsenic Research: Past, Present, and Future 469
Iain L. Cartwright

22 Toxicokinetics and Pharmacokinetic Modeling of Arsenic 495
Elaina M. Kenyon and Harvey J. Clewell, III

23 Considerations for a Biologically Based Risk Assessment for Arsenic 511
Harvey J. Clewell, III, P. Robinan Gentry and Janice W. Yager

24 Translating Experimental Data to Human Populations 535
J. Christopher States

Index 549

J. Christopher States, PhD, is Professor, University Scholar and Vice Chair for Graduate Education in the Department of Pharmacology and Toxicology, and Associate Dean for Research in the University of Louisville School of Medicine, Louisville, Kentucky. He is a Past President of the Society of Toxicology Metals Specialty Section, on the editorial board of several leading journals, and regularly serves as a reviewer of manuscripts and National Institutes of Health grants. He has organized symposia and workshops and chaired sessions on arsenic exposure and toxicology at international conferences and published over 100 articles. Although used in pesticides and wood preservatives, arsenic is potentially fatal at high levels and creates a toxicological concern around the world – according to one study, over 140 million people in more than 70 countries are affected by arsenic contamination of drinking water. Exposure to high levels of arsenic also occurs in workplaces and near hazardous waste sites, and long-term exposure is often associated with several types of cancer and death from other chronic diseases. Despite the known effects of arsenic and regulatory guidelines to deal with it, there are increasing reports and evidential research that indicate more health risks and growing concerns.

This book discusses arsenic’s fundamentals, exposure sources, epidemiology and disease, and toxic mechanisms. It illustrates the chemistry, toxicology, and health effects of arsenic using novel modeling techniques, population studies, experimental data, and future perspectives. It illustrates the chemistry, toxicology, and health effects of arsenic so that readers will come away with an understanding about the potential health risks and ways that toxicological research can improve and contribute to characterization and risk assessment of arsenic exposure.

An invaluable resource and reference for toxicologists, environmental chemists, and risk assessors; this book offers:

Population studies, mammalian and invertebrate models, and pharmacokinetic and toxicokinetic models

Discussion of outcomes, epidemiology, real-life examples, and modes of action for arsenic-induced diseases, like lung cancer, diabetes, and cardiovascular and pulmonary diseases

Future perspectives on special topics, like extrapolation from experimental models to human exposures, biomarkers for phenotypic anchoring, and pathology of chronic exposure