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The Dose Makes the Poison: A Plain-Language Guide to Toxicology, 3rd Edition

ISBN: 978-0-470-38112-0
284 pages
March 2011
The Dose Makes the Poison: A Plain-Language Guide to Toxicology, 3rd Edition (0470381124) cover image
This new edition of a widely-read and highly-acclaimed book broadens the scope of its predecessors from a heavy focus on industrial chemicals as toxicants to include drugs, food additives, cosmetics and other types of compounds that people are exposed to daily. Also new to the 3rd edition are newer issues-of-the-day such as nanoparticulate toxicants, second hand smoke, food contamination, lead in toys, and others. As such, the book provides the basics of toxicology in easy-to-understand language as well as a fuller understanding of the daily insults to which our bodies are subjected.
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Introduction to the Third Edition xi

Preface to the Second Edition xv

1 WHAT ARE CHEMICALS? 1

Atoms and Molecules 1

Natural Chemicals 2

Synthetic Chemicals 3

Chemical Categories 6

Chemicals: “Good” and “Bad” 8

Why the “Good-Bad” Dichotomy? 10

Man-made Chemicals Are Made by Humans 11

Man-made Chemicals May Not Be Biodegradable 12

Man-made Chemicals May Be Very Complex 16

2 WHAT HARM DO CHEMICALS CAUSE? 19

Harmful Properties of Chemicals 19

Explosiveness and Reactivity 19

Flammability and Combustibility 20

Radioactivity 21

Corrosiveness 23

Irritation 23

Sensitization and Photosensitization 24

Toxicity 26

Multiple Harmful Properties 27

Definition of Poison 28

Defi nition of Hazard 28

3 WHAT IS TOXICOLOGY? 31

Empirical Toxicology 31

Paracelsus and Ramazzini 32

A Brief History of Toxicology 34

Toxicology Today 40

What Do Toxicologists Do? 44

4 WHAT FACTORS INFLUENCE THE TOXIC EFFECTS OF CHEMICALS? 47

Acute versus Chronic Toxicity 47

Significance of Divided Doses 53

Routes of Exposure 54

Dermal Exposure 54

Inhalation Exposure 55

Oral Exposure 58

Other Routes of Exposure 59

Combinations 60

Influence of Route on Toxicity 60

Metabolism 64

Routes of Elimination (Excretion) 65

Other Factors that Infl uence Toxicity 66

Species 66

Sex 70

Age 71

Nutrition 73

State of Health 73

Biochemical Individuality (Genetic Diversity) 74

Presence of Other Chemicals 75

Adaptation 77

Light 79

5 HOW IS TOXICOLOGY STUDIED? 81

Experimental Methods 82

Acute Toxicity 83

Irritant and Corrosive Effects 85

Sensitization and Photosensitization 86

Chronic Toxicity 87

Mutagenesis 90

Carcinogenesis 91

Developmental and Reproductive Toxicity 94

Units of Trace Quantities 95

Analytical Methods 96

Animal Rights 99

6 GENERAL TOXICOLOGY 103

Acute Toxicity 103

LD50 and LC50 Values 103

Signifi cance of LDs for Humans 104

Poison Prevention 109

Antidotes 112

Chronic Toxicity 114

No-Effect Levels and Thresholds 116

Margins of Safety 117

Sufficient Challenge 119

Bioaccumulation 121

7 MUTAGENESIS AND CARCINOGENESIS 129

Mutagenesis 129

Genetic Code 129

Mutations 130

Significance of Mutations 132

Mutation and Cancer 135

Carcinogenesis 138

What Is Cancer? 138

Causes of Cancer 140

Role of Mutation 141

Incidence of Cancer 142

Categories and Characteristics of Carcinogens 143

Induction Periods 146

Thresholds 147

Practical Thresholds 149

The Real World 150

Benzo[a]pyrene 150

Cancerophobia 151

8 DEVELOPMENTAL AND REPRODUCTIVE TOXICITY 153

Male and Female Reproductive Systems 154

Prepuberty Systems 154

Adult Systems 155

The Developing Individual 156

9 CASE STUDIES IN TOXICOLOGY 163

Environmental Contaminations 164

Dioxins: Seveso, Italy 164

PCBs and Dibenzofurans: Yusho Disease 169

Bophal, India 173

Minamata Disease 174

DDT 174

Consumer Products 177

Metals 177

Lead and Cadmium 178

Zinc 178

Plastics 179

Bisphenyl A 180

Indoor Air Pollution 181

Water Pollution 185

Pharmaceuticals 186

Fen-Phen 187

Vioxx 188

Thalidomide 189

10 EPIDEMIOLOGY 191

Origins of Modern Epidemiology 191

Epidemiology of Noninfectious Diseases 193

Koch’s Postulates 195

Study Design: Precepts and Pitfalls 197

Unreasonable Expectations 201

Proximate Event Approach in Assigning Cause 202

Distrust of Science and Scientists 204

11 THE STUDY OF RISK 211

Public Health Statistics 211

Inherent Risk 213

Risk Assessment 215

Perceived Risk 218

Acceptable Risk 220

Risk Benefit and Cost Benefit 222

Risk Communication 225

Risk Management 227

Bibliography 229

Abbreviations 233

Glossary 235

Appendix A 245

Index 247

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Patricia Frank is President of Patricia Frank & Associates, Inc., a consulting firm founded in 1993 that assists companies in the development and registration of human and veterinary pharmaceutical agents. She is a past president of both the American College of Toxicology and the Roundtable of Toxicology Consultants.

M. Alice Ottoboni lectures, writes, and consults in the field of toxicology. As Staff Toxicologist with the California State Department of Public Health for over twenty years, she originated, designed, and performed numerous toxicological studies of environmental factors of importance to public health. She is the author of the previous editions of The Dose Makes the Poison.

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"This is a refreshing, invigorating as well as eye-opening text, which is reading like an exciting novel - even to a seasoned toxicologist ... An appendix to clarify quantities of pollutants plus an index concludes this most valuable introduction into the science of toxicology for a broad readership." (Toxicology, 2011)

"I recommend this book to anyone who has ever listened to the evening news and wondered how much of the "chemical scare du jour" is hype and how much of it is fact - and to those who might want to understand basic concepts in toxicology and the related areas of study without having to trudge through a gaggle of 1000-page textbooks." (International Journal of Toxicology, 2011)

"Overall, this is a well-written work with wisely chosen and relevant topics. It will be a perfect addition to any science enthusiast's library. Summing Up: Highly recommended. Lower-level undergraduates through professionals/practitioners; general readers." (Choice, 1 September 2011)

"The Dose Makes the Poison is more than just an introduction to toxicology. It is an enjoyable read with lots of interesting stories and one I can thoroughly recommend." (Chemistry & Industry, 25 July 2011)

"There is much to be applauded in this book from its straightforward layout and honesty to its accessibility . . . Many good, and contemporary, examples are provided to deliver greater context for the reader." (The British Toxicology Society Journal, 1 May 2011) 

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February 17, 2011
The Dose Makes the Poison: A Plain-Language Guide to Toxicology, 3rd Edition

Toxins are a burning issue. A straightforward guide to a closer understanding of toxins in our daily lives is published by Wiley (March 2011). The Dose Makes the Poison: A Plain-Language Guide to Toxicology, 3rd Edition cuts through the fear generated by the media, which leads to a distortion in many people’s conceptions of toxins and chemicals.

The word “toxin” fills many of us with dread. We are exposed to media reports on a daily basis of the damage done to our bodies and to the environment by toxins. Pesticides, food additives, cosmetics, drugs and second-hand smoke are just some of the toxins we are subjected to day in day out, not to mention industrial chemicals. The constant barrage of media reports have led to a general fear of toxins, and of chemicals in general.

The Dose Makes the Poison tells you in clear and simple terms what is and what is not a toxin, and, taking a measured approach, dispels the fear. Toxins are chemicals - every substance in the world is made up of chemicals, whether man-made or naturally-occurring. But what makes a chemical a toxin is the dose, not the chemical itself, whether man-made or naturally-occurring.

The Dose Makes the Poison explains the basics and practice of toxicology, using clear examples from everyday life. One example is the common misconception that naturally-occurring chemicals are not as harmful to us as those that are man-made – botulin is one of the most highly toxic chemicals in existence and is made by bacteria. Another example is the presence in all food (including organic food), of potentially harmful natural chemicals, which only become toxins when in a high enough dose.

This is the third edition of a best-selling book, now with broader scope and updated to include current issues such as drug recalls, food contamination and nanoparticulate toxicants.

A thoroughly accessible and objective discussion of toxicology, The Dose Makes the Poison will be of great interest to all readers, even with no strong science background. It is a must-read for professionals including toxicologists, industrial hygienists, regulatory personnel, product safety workers, and health professionals.

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by John L. LaMattina, Patricia Frank, M. Alice Ottoboni
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