The Dose Makes the Poison: A Plain-Language Guide to Toxicology, 3rd Edition PDF
Preview The Dose Makes the Poison: A Plain-Language Guide to Toxicology, 3rd Edition
ffffiirrss..iinndddd iiii 1122//1166//22001100 77::5544::4400 PPMM THE DOSE MAKES THE POISON ffffiirrss..iinndddd ii 1122//1166//22001100 77::5544::4400 PPMM ffffiirrss..iinndddd iiii 1122//1166//22001100 77::5544::4400 PPMM THE DOSE MAKES THE POISON A Plain-Language Guide to Toxicology THIRD EDITION PATRICIA FRANK, PH.D. M. ALICE OTTOBONI, PH.D. A JOHN WILEY & SONS, INC., PUBLICATION ffffiirrss0022..iinndddd iiiiii 1122//1166//22001100 77::5544::4411 PPMM Copyright © 2011 by Patricia Frank and M. Alice Ottoboni. All rights reserved. Published by John Wiley & Sons, Inc., Hoboken, New Jersey Published simultaneously in Canada No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400, fax 978-750-4470, or on the web at www. copyright.com. Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, 201- 748-6011, fax 201-748-6008, or online at http://www.wiley.com/go/permission. Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifi cally disclaim any implied warranties of merchantability or fi tness for a particular purpose. No warranty may be created or extended by sales representatives or written sales materials. The advice and strategies contained herein may not be suitable for your situation. You should consult with a professional where appropriate. Neither the publisher nor author shall be liable for any loss of profi t or any other commercial damages, including but not limited to special, incidental, consequential, or other damages. For general information on our other products and services or for technical support, please contact our Customer Care Department within the United States at 877-762-2974, outside the United States at 317-572-3993 or fax 317-572-4002. Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic formats. For more information about Wiley products, visit our web site at www.wiley.com. Library of Congress Cataloging-in-Publication Data: Frank, Patricia. The dose makes the poison : a plain-language guide to toxicology / Patricia Frank, M. Alice Ottoboni. – 3rd ed. p. cm. Includes bibliographical references and index. Prev. ed., published in 1991, entered under M. Alice Ottoboni. ISBN 978-0-470-38112-0 (pbk.) 1. Toxicology–Popular works. I. Ottoboni, M. Alice. II. Ottoboni, M. Alice. Dose makes the poison. III. Title. RA1213.O88 2011 615.9–dc22 2010023287 Printed in Singapore oBook ISBN: 978-0-470-91844-9 ePDF ISBN: 978-0-470-91843-2 ePub ISBN: 978-0-470-92273-6 10 9 8 7 6 5 4 3 2 1 ffffiirrss0022..iinndddd iivv 1122//1166//22001100 77::5544::4411 PPMM CONTENTS 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 Defi nition of Poison 28 Defi nition of Hazard 28 3 WHAT IS TOXICOLOGY? 31 Empirical Toxicology 31 Paracelsus and Ramazzini 32 v ffttoocc..iinndddd vv 1122//1166//22001100 77::5544::4433 PPMM vi CONTENTS 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 Signifi cance of Divided Doses 53 Routes of Exposure 54 Dermal Exposure 54 Inhalation Exposure 55 Oral Exposure 58 Other Routes of Exposure 59 Combinations 60 Infl uence 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 ffttoocc..iinndddd vvii 1122//1166//22001100 77::5544::4433 PPMM CONTENTS vii Analytical Methods 96 Animal Rights 99 6 GENERAL TOXICOLOGY 103 Acute Toxicity 103 LD and LC Values 103 50 50 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 Suffi cient Challenge 119 Bioaccumulation 121 7 MUTAGENESIS AND CARCINOGENESIS 129 Mutagenesis 129 Genetic Code 129 Mutations 130 Signifi cance 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 ffttoocc..iinndddd vviiii 1122//1166//22001100 77::5544::4433 PPMM viii CONTENTS 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 Benefi t and Cost Benefi t 222 Risk Communication 225 Risk Management 227 ffttoocc..iinndddd vviiiiii 1122//1166//22001100 77::5544::4433 PPMM
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