Risk Assessment for Human Metal Exposures: Mode of Action and Kinetic Approaches examines the current principles of risk assessment in human metal exposures, with a focus on Mode of Action(MOA), Toxicokinetic and Toxicodynamic (TKTD) considerations, and computer models. Derived from the highly respected Handbook on the Toxicology of Metals, Fourth Edition (2014), the book summarizes principles and methods and provides examples of how MOA –TKTD can be used. In addition, it presents tactics on how information generated by such methods can be confirmed by epidemiological data. Furthermore, it demonstrates how epidemiological data can be confirmed and evaluated by the examined models and considerations.
This resource uniquely integrates several important topics, such as risk assessment, characterization, management and communication—the classic risk assessment paradigm—with mode of action, TKTD, and epidemiology, all topics related to human exposure. Written by pioneers in the field, this book is an essential reference for researchers, students and technicians in toxicology and risk assessment.
- Covers fundamental risk assessment concerns for the effects of metals on human health
- Provides an easy-to-use structure to quickly locate specific methods
- Uses case studies to illustrate the methods and theories described
- Written to be understood by students, researchers and industry workers who need to conduct risk assessment in metals and human health
Arvustused
"Risk Assessment for Human Metal Exposures is a timely publication that covers all aspects of risk assessment of metals, and provides a clear description of recent developments, novel approaches, and their application in evaluating risks of exposure to metals, be they essential trace metals purely toxic ones. New approaches covered include toxicokinetic/toxicodynamic models, biomonitoring strategies, Mode of Action (MoA) assessment, and Adverse Outcome Pathways (AOP) approaches, as well as mechanism of action considerations and specific approaches to the use of human data, particularly from epidemiological studies. It is an excellent piece of work, and a recommended read for risk assessment professionals." --Prof. Dr. Maged Younes, Former Director at WHO and UNEP
"This book is an application of the combination of scientific information over time and the rich experience by the authors of risk assessment of metals for the health of humans. I would like to recommend to students, teachers, researchers and scientists working in toxicology and environmental epidemiology" --Taiyi Jin, MD, PhD, Professor and former Chair of the Department of Occupational Health and Toxicology, School of Public Health , Fudan University, Shanghai, China
"It is my pleasure to recommend the book, Risk Assessment for Human Metal Exposure: Mode of Action and Kinetic Approaches by Gunnar F. Nordberg and Bruce A. Fowler. The book is useful for both beginner and the advanced toxicologists. It presents information on the toxicology of metals in relation to human exposure, risk assessment, and health effects of the most widespread metal in occupational settings in a very concise way
...It will be an asset for toxicologists, occupational hygienists, physicians, pharmaceutists, and students who want to broaden their knowledge further, as well as for those experienced readers who need to have access to the most current guidelines and methods of risk assessment.The authors, who are recognized experts in the field of metal toxicology, guarantee up-to-date information and current knowledge." --Natalia Pawlas, MD, PhD, Associate Professor, Medical University of Silesia, Poland, Scientific Committee on Toxicology of Metals, ICOH
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| Preface |
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1 Metal Exposures and Human Health--Historical Development, Current Importance, and Toxicological Concepts for Prevention |
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1 | (30) |
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2 | (1) |
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1.2 Widespread Exposure to Metals Contributes to Global Burden of Disease |
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3 | (1) |
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1.3 Metal Poisoning---Clinical Symptoms and Signs in Occupational and Environmental Settings |
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4 | (2) |
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1.4 Detailed Investigation Is Required for Identification of Adverse Effects at Low-Level Metal Exposures |
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6 | (2) |
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1.5 Perspectives on Historical Development of Concepts Used in Risk Assessment of Metal Exposures---Role of the Scientific Committee on the Toxicology of Metals |
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8 | (3) |
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1.6 Current Long-Term Low-Level Exposures and Related Health Effects |
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11 | (3) |
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1.7 Issues of Current Concern for Hazard Assessment, Risk Assessment, and Prevention |
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14 | (17) |
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26 | (5) |
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2 Exposure, Internal Dose, and Toxicokinetics (TK) |
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31 | (44) |
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2.1 Introduction; Terminology |
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31 | (3) |
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34 | (6) |
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2.3 Deposition and Absorption |
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40 | (13) |
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2.4 Transport, Biotransformation, and Distribution |
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53 | (3) |
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56 | (6) |
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62 | (7) |
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2.7 Use of Indicator Media for Estimating Critical Organ Concentration |
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69 | (6) |
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70 | (5) |
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3 Biomonitoring, Mode of Action (MOA), Target Dose, and Adverse Outcome Pathways (AOPs) |
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75 | (24) |
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75 | (1) |
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3.2 General Considerations on Exposure, Environmental, and Biological Monitoring |
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76 | (3) |
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79 | (8) |
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3.4 Mechanism of Action, Mode of Action, and Adverse Outcome Pathways as a Basis for Hazard and Risk Assessment |
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87 | (9) |
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96 | (3) |
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96 | (3) |
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4 Hazard Identification and Assessment |
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99 | (34) |
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99 | (2) |
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101 | (1) |
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4.3 Mechanism of Action, Mode of Action, and Adverse Outcome Pathways |
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102 | (3) |
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105 | (7) |
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4.5 Data From Studies on Acute and Chronic Toxicity in Animals, Cells, and Molecular Systems In Vitro; Computational Systems |
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112 | (7) |
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4.6 Observations of Carcinogenicity of Metallic Compounds During 40 Years |
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119 | (3) |
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4.7 Carcinogenicity Classification by National/Union Authorities and by Other Organizations |
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122 | (3) |
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4.8 Ethical Considerations for Studies of Effects of Chemical Compounds With Humans or Animals |
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125 | (8) |
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130 | (3) |
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5 Dose--Effect and Dose--Response Assessment |
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133 | (24) |
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5.1 Concepts in Quantitative Toxicological Analysis |
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133 | (10) |
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5.2 Estimating Acceptable or Recommended Exposure Levels in Humans Based on Dose-Response Studies in Animals |
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143 | (6) |
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5.3 Dose--Response Relationships Based on Mechanism of Action, Toxicokinetic and Toxicodynamic Modeling, and Adverse Outcome Pathways |
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149 | (1) |
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5.4 Dose--Response Assessment Based on Epidemiological Studies |
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150 | (3) |
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153 | (4) |
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6 Dose--Response for Essential Metals and the Evaluation of Mixed Exposures |
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157 | (42) |
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6.1 Essentiality of Trace Metals |
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167 | (3) |
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6.2 Defining an Acceptable Range of Oral Intakes |
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170 | (3) |
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6.3 Other Terms and Concepts Used in Risk Assessment of Essential Trace Metals |
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173 | (2) |
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6.4 Basic Mechanisms of Homeostasis |
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175 | (1) |
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6.5 Health Effects of Deficiency and Excess |
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176 | (1) |
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6.6 Examples of Effects of Varying Severity |
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177 | (5) |
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6.7 Summary and Conclusions on the Principles of Risk Assessment for Human Exposures to Essential Trace Metals |
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182 | (2) |
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6.8 The Influence of Essential Metals on Effects and Dose--Response Relationships of Toxic Metals |
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184 | (2) |
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6.9 The Combined Action of Metal Compounds, Including Interactions, Principles, and Methods of Assessment |
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186 | (2) |
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6.10 The Action of Other Factors Than Essential Metals on the Effects of Metallic Compounds |
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188 | (2) |
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6.11 Gene---Environment Interactions |
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190 | (2) |
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6.12 Evaluation of Exposure to Mixtures |
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192 | (7) |
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194 | (5) |
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7 Applied Risk Assessment, Hazard Assessment, and Risk Management |
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199 | (28) |
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199 | (1) |
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7.2 Risk Characterization |
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200 | (7) |
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207 | (14) |
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221 | (1) |
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222 | (1) |
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7.6 Examples of Successful Prevention of Adverse Health Effects |
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223 | (4) |
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224 | (3) |
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8 Examples of Risk Assessments of Human Metal Exposures and the Need for Mode of Action (MOA), Toxicokinetic-Toxicodynamic (TKTD) Modeling, and Adverse Outcome Pathways (AOPs) |
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227 | (84) |
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228 | (5) |
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233 | (8) |
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241 | (14) |
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255 | (7) |
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262 | (2) |
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264 | (2) |
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8.7 The Lanthanides (Including Lanthanum, La; Cerium, Ce; and Gadolinium, Gd) |
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266 | (7) |
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273 | (4) |
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277 | (10) |
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287 | (11) |
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298 | (3) |
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301 | (10) |
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305 | (6) |
| Appendix |
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311 | (8) |
| Index |
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319 | |
Dr Gunnar F. Nordberg, MD, PhD, is an emeritus Professor at Umea University, Umea, Sweden, where he served as chairman of the Department of Environmental and Occupational Medicine for many years. He has also worked as a Professor and chair at the Department of Environmental Medicine, Odense University, Denmark and for periods of a year at the International Agency for Research on Cancer, Lyon, France and the University of North Carolina and the National Institute of Environmental Health Sciences, NC, USA. In his capacity as university professor, he tutored many PhD and master students in Environmental medicine, a number of them from countries around the world. He has published more than 300 papers in Scientific Journals and International Handbooks. In addition, he authored, edited or co-edited 24 Scientific Books and participated in International Task Groups evaluating Risks of Environmental Agents, which resulted in 30 international books or reports. Some of these publications resulted from his activities as a chairman of the Scientific Committee on the Toxicology of Metals, International Commission on Occupational Health. He is presently the Task Group Chairman of Cadmium Risk Assessment in the Toxicology and Risk Assessment Group of the International Union of Pure and Applied Chemistry. His Scientific Publications are mainly on Toxicology and Epidemiology of environmental agents, particularly metals and the application of such data for Human Risk Assessment. He has coordinated EU- projects on Environmental Epidemiology and Toxicology of Metals and participated as an active scientist in several such projects. He has been the principal investigator of many research projects funded by Swedish funding Agencies and is presently actively involved in such research. He is one of the editors of a Textbook in Swedish Arbets- och Miljömedicin”, latest 4th edition 2019. Chief Editor, Handbook on the Toxicology of Metals, 5th Ed, published 2021 by Academic Press/Elsevier. He has extensive experience as an expert serving Swedish and International Authorities, such as the Swedish National Board of Health (Socialstyrelsen), Japan Food Safety Agency, US Environmental Protection Agency, National Institute of Environmental Health Sciences (NIEHS), Agency for Toxic Substances and Disease Registry (ATSDR) USA, World Health Organization HQ, Geneva/International Program on Chemical Safety/WHO Commission on Health and the Environment, Energy Panel; International Agency for Research on Cancer IARC, Lyon, France, Europe/European Environment Agency, Copenhagen; European Medicines Agency, London; European Food Safety Authority (EFSA), Parma, Italy. Dr. Fowler began his scientific career at the National Institute of Environmental Health Sciences prior to becoming Director of the University of Maryland System-wide Program in Toxicology and Professor at the University of Maryland School of Medicine. He then served as Associate Director for Science in the Division of Toxicology and Environmental Medicine at Agency for Toxic Substances and Disease Registry (ATSDR). He is currently a private consultant and Co-owner of Toxicology Risk Assessment Consulting Services (TRACS), LLC. In addition, Dr. Fowler serves as an Adjunct Professor, Emory University Rollins School of Public Health and Presidents Professor of Biomedical Sciences, Center for Alaska Native Health Research (CANHR) at the University of Alaska- Fairbanks. Dr. Fowler, is an internationally recognized expert on the toxicology of metals and has served on a number of State, National and International Committees in his areas of expertise. These include the Maryland Governors Council on Toxic Substances (Chair), various National Academy of Sciences / National Research Council Committees, including the 1993 landmark NAS/NRC Report on Measuring Lead Exposure in Infants Children and Other Sensitive Populations” for which he served as the Committee Chair. He has also served on a number of review committees of the National Institutes of Health, the USEPA Science Advisory Board and the Fulbright Scholarship review committee for Scandinavia (Chair, 2000-2001). In 2016, he became an Inaugural Member of the Fulbright 1946 Society and in 2018 became a member of the Fulbright Association Board of Directors. He has also served as a temporary advisor to the World Health Organization (WHO) and on working groups of the International Agency for Research Against Cancer (IARC) for a number of toxicology and risk assessment issues. He is presently appointed as a member of the Joint FAO/WHO Expert Committee on Food Additives (JECFA) for the period 2016-2020. Dr. Fowler has been honored as a Fellow of the Japanese Society for the Promotion of Science (JSPS), a Fulbright Scholar and Swedish Medical Research Council Visiting Professor at the Karolinska Institute, Stockholm, Sweden and elected as a Fellow of the Academy of Toxicological Sciences. His more recent awards include a CDC/ATSDR, Honor Award for Excellence in Leadership Award 2010, The US Pharmacopea (USP) Toxicology Committee 2010-2015 and the USP Elemental Impurities Panel which received the 2014 U.S. Pharmacopea Award for an Innovative Response to Public Health Challenges (Group Award). He is currently appointed to the USP Nanotechnology Subcommittee 2015-. Dr. Fowler was previously elected to the Council of the Society of Toxicology (2005-2007), the Board of Directors of the Academy of Toxicological Sciences (2006-2009), and more recently, to the Council of the Society for Risk Analysis (2014-2017). He is the Federal Legislative and National Active and Retired Federal Employees Association and (NARFE)-PAC Chair for the Rockville Maryland Chapter of NARFE and is currently Chair of the Federal Legislative Committee for the Maryland NARFE Federation. Dr. Fowler is the Past- President of the Rotary Club of North Bethesda, Maryland (2016-2017) and was selected as Rotarian of the Year in 2015 for his work in developing a taxi-based program to help persons with disabilities gain independence via reliable transportation to work. Dr. Fowler is the author of over 260 research papers and book chapters dealing with molecular mechanisms of metal toxicity, molecular biomarkers for early detection of metal-induced cell injury and application of computational toxicology for risk assessment. He has been the editor, co-editor or author of 10 books or monographs on metal toxicology and mechanisms of chemical induced cell injury, molecular biomarkers and risk assessment and computational toxicology. Dr. Fowler is currently focused on the global problem of electronic waste (e-waste) in developing countries. He serves on the editorial boards of a number of scientific journals in toxicology and is an Associate Editor of the journal Toxicology and Applied Pharmacology and a past Associate Editor of Environmental Health Perspectives (2007-2016).
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