A Textbook of Modern Toxicology, 4th Edition.PDF
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1、A TEXTBOOK OF MODERN TOXICOLOGYA TEXTBOOK OF MODERN TOXICOLOGYFOURTH EDITIONEdited byErnest HodgsonNorth Carolina State UniversityRaleigh,North CarolinaA JOHN WILEY&SONS,INC.,PUBLICATIONCopyright 2010 John Wiley&Sons,Inc.All rights reserved.Published by John Wiley&Sons,Inc.,Hoboken,New Jersey.Publis
2、hed 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,w
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4、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:/ of Liability/Disclaimer of Warranty:While the publisher and author have used their best efforts in preparing this book,they make no representations or war
5、ranties 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 strate
6、gies 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 damage
7、s.For general information on our other products and services or for technical support,please contact our Customer Care Department within the United States at(800)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.S
8、ome content that appears in print may not be available in electronic formats.For more information about Wiley products,visit our web site at .Library of Congress Cataloging-in-Publication Data:A textbook of modern toxicology/edited by Ernest Hodgson.4th ed.p.cm.ISBN 978-0-470-46206-5(cloth)1.Toxicol
9、ogy.I.Hodgson,Ernest,1932 RA1211.H62 2010 615.9dc22 2009045883Printed in the United States of America10 9 8 7 6 5 4 3 2 1CONTENTSPREFACE TO THE FOURTH EDITION xxiCONTRIBUTORS xxiiiPART I INTRODUCTION 11.Introduction to Toxicology 3Ernest Hodgson1.1 Defi nition and Scope 31.2 Relationship to Other Sc
10、iences 91.3 A Brief History of Toxicology 101.4 DoseResponse Relationships 111.5 Sources of Toxic Compounds 121.6 Movement of Toxicants in the Environment 12Bibliography and Suggested Reading 13Sample Questions 142.Introduction to Biochemical and Molecular Methods in Toxicology 15Ernest Hodgson,Gera
11、ld A.Leblanc,Sharon A.Meyer,and Robert C.Smart2.1 Introduction 152.2 Cell Culture Techniques 152.2.1 Suspension Cell Culture 162.2.2 Monolayer Cell Culture 162.2.3 Indicators of Toxicity in Cultured Cells 162.2.4 Use of Stem Cells 172.2.5 Cell Culture Models as“Alternative”Toxicity Tests 192.3 Molec
12、ular Techniques 192.3.1 Molecular Cloning 202.3.2 cDNA and Genomic Libraries 202.3.3 Northern and Southern Blot Analysis 212.3.4 PCR 222.3.5 Evaluation of Gene Expression,Regulation,and Function 222.4 Immunochemical Techniques 232.5 Proteomics 262.6 Metabolomics 262.7 Bioinformatics 262.8 Summary an
13、d Conclusions 27vvi CONTENTSBibliography and Suggested Reading 27Sample Questions 27PART II CLASSES OF TOXICANTS 29 3.Exposure Classes,Toxicants in Air,Water,Soil,Domestic,and Occupational Settings 31W.Gregory Cope3.1 Air Pollutants 313.1.1 History 313.1.2 Types of Air Pollutants 323.1.3 Sources of
14、Air Pollutants 333.1.4 Examples of Air Pollutants 343.1.5 Environmental Effects 373.2 Water and Soil Pollutants 383.2.1 Sources of Water and Soil Pollutants 383.2.2 Examples of Pollutants 393.3 Occupational Toxicants 423.3.1 Regulation of Exposure Levels 433.3.2 Routes of Exposure 443.3.3 Examples o
15、f Industrial Toxicants 44Bibliography and Suggested Reading 46Air Pollutants 46Water and Soil Pollutants 47Occupational Toxicants 47Sample Questions 474.Classes of Toxicants:Use Classes 49W.Gregory Cope and Ernest Hodgson4.1 Introduction 494.2 Metals 494.2.1 History 494.2.2 Common Toxic Mechanisms a
16、nd Sites of Action 504.2.3 Lead 514.2.4 Mercury 524.2.5 Cadmium 534.2.6 Chromium 534.2.7 Arsenic 544.2.8 Treatment of Metal Poisoning 544.3 Agricultural Chemicals(Pesticides)554.3.1 Introduction 554.3.2 Defi nitions and Terms 564.3.3 Organochlorine Insecticides 59CONTENTS vii4.3.4 Organophosphorus(O
17、P)Insecticides 604.3.5 Carbamate Insecticides 614.3.6 Botanical Insecticides 614.3.7 Pyrethroid Insecticides 624.3.8 New Insecticide Classes 624.3.9 Herbicides 624.3.10 Fungicides 644.3.11 Rodenticides 644.3.12 Fumigants 654.3.13 Conclusions 654.4 Food Additives and Contaminants 654.5 Toxins 664.5.1
18、 History 664.5.2 Microbial Toxins 674.5.3 Mycotoxins 674.5.4 Algal Toxins 684.5.5 Plant Toxins 694.5.6 Animal Toxins 704.6 Solvents 714.7 Therapeutic Drugs 714.8 Drugs of Abuse 724.9 Combustion Products 724.10 Cosmetics 74Bibliography and Suggested Reading 74General 74Metals 74Pesticides 75Toxins 75
19、Solvents 75Therapeutic Drugs 75Sample Questions 75PART III TOXICANT PROCESSING IN VIVO 775.Absorption and Distribution of Toxicants 79Ronald E.Baynes and Ernest Hodgson5.1 Introduction 795.2 Cell Membranes 805.3 Mechanisms of Transport 825.3.1 Passive Diffusion 835.3.2 Carrier-Mediated Membrane Tran
20、sport 865.4 Physicochemical Properties Relevant to Diffusion 875.4.1 Ionization 885.4.2 Partition Coeffi cients 89viii CONTENTS5.5 Routes of Absorption 905.5.1 Extent of Absorption 915.5.2 Gastrointestinal Absorption 925.5.3 Dermal Absorption 945.5.4 Respiratory Penetration 975.6 Toxicant Distributi
21、on 995.6.1 Physicochemical Properties and Protein Binding 995.6.2 Vd 1065.7 Toxicokinetics 108Bibliography and Suggested Reading 112Sample Questions 1136.Metabolism of Toxicants 115Ernest Hodgson and Randy L.Rose6.1 Introduction 1156.2 Phase I Reactions 1166.2.1 The Endoplasmic Reticulum,Microsomes,
22、and Monooxygenations 1166.2.2 The CYP-Dependent Monooxygenase System 1186.2.3 The FMO 1326.2.4 Nonmicrosomal Oxidations 1356.2.5 Co-oxidation by Cyclooxygenase(COX)1376.2.6 Reduction Reactions 1386.2.7 Hydrolysis 1406.2.8 Epoxide Hydration 1426.2.9 DDT Dehydrochlorinase 1436.3 Phase II Reactions 143
23、6.3.1 Glucuronide Conjugation 1436.3.2 Glucoside Conjugation 1456.3.3 Sulfate Conjugation 1456.3.4 Methyltransferases 1476.3.5 GSTs and Mercapturic Acid Formation 1496.3.6 Cysteine Conjugate-Lyase 1516.3.7 Acylation 1526.3.8 Phosphate Conjugation 154Bibliography and Suggested Reading 154Sample Quest
24、ions 1557.Reactive Metabolites 157Ernest Hodgson and Randy L.Rose7.1 Introduction 1577.2 Activation Enzymes 1587.3 Nature and Stability of Reactive Metabolites 1607.4 Fate of Reactive Metabolites 1617.4.1 Binding to Cellular Macromolecules 1617.4.2 Lipid Peroxidation 161CONTENTS ix7.4.3 Trapping and
25、 Removal:Role of Glutathione 1627.4.4 Trapping and Removal:Role of Epoxide Hydration 1627.5 Factors Affecting Toxicity of Reactive Metabolites 1627.5.1 Levels of Activating Enzymes 1637.5.2 Levels of Conjugating Enzymes 1637.5.3 Levels of Cofactors or Conjugating Chemicals 1637.6 Reactive Oxygen Spe
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