Concepts In Inhalation Toxicology PDF
Preview Concepts In Inhalation Toxicology
CONCEPTS IN INHALATION TOXICOLOGY CONCEPTS IN INHALATION TOXICOLOGY Second Edition Edited by Roger 0. McClellan Chemical Industry Institute of Toxicology Research Triangle Park, North Carolina Rogene F. Henderson Inhalation Toxicology Research Institute Lovelace Biomedical and Environmental Research Institute Albuquerque, New Mexico informa healthcare New York London CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 1995 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Version Date: 20130325 International Standard Book Number-13: 978-1-4398-0557-2 (eBook - PDF) This book contains information obtained from authentic and highly regarded sources. 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Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com Contents Contributors Xlll Foreword XV Preface xxi Preface to the First Edition xxiii PART 1: INTRODUCTION Chapter 1 An Introduction to Inhalation Toxicology 3 Roger 0. McClellan Concern about Air Pollution 4 Orientations to Inhalation Toxicology 13 Sources of Information 16 Organization of the Book 17 Summary 20 Acknowledgments 20 References 21 PART 2: INHALATION EXPOSURE Chapter 2 Inhalation Exposure Systems 25 Yung-Sung Cheng and Owen R. Moss Introduction 25 Exposure Systems 27 Exposure Chambers 31 Evaluation of Exposure Chambers 45 Environmental Conditions within Exposure Chambers 54 Facilities 59 Summary 60 Acknowledgment 61 References 61 v vi CONTENTS Chapter 3 Generation and Characterization of Gases and Vapors 67 Brian A. Wong Introduction 67 Concentration Units 68 Basic Considerations 71 Generation 73 Gas Control 82 Characterization of Gas Concentration 85 Automation and Computer Control 88 Summary 89 References 89 Chapter 4 Generation and Characterization of Test Atmospheres: Particles and Droplets 91 Owen R. Moss and Yung-Sung Cheng Introduction 91 Basic Properties of Particles 92 Particle Size 95 Generation of Aerosols 102 Characterizing Airborne Particles Ill Summary 121 Acknowledgment 122 References 122 Bibliography 125 PART 3: BASIC BIOLOGY OF THE RESPIRATORY TRACT Chapter 5 Morphology of the Respiratory Tract 129 Robert F. Phalen, Hsu-Chi Yeh, and Shankar B. Prasad Introduction 129 Respiratory-Tract Regions 130 Gross Anatomy 133 Cells and Tissues of the Respiratory Tract 138 The Lymphatic System 143 Innervation of the Respiratory System 145 Postnatal Lung Development 146 Summary 147 References 147 CONTENTS vii Chapter 6 Lung Biochemistry and Intermediary Metabolism for Concepts in Inhalation Toxicology 151 Aron B. Fisher Lung Biochemistry and Intermediary Metabolism 151 Summary 169 Acknowledgments 169 References 169 Chapter 7 Metabolic Characteristics of the Respiratory Tract 175 Alan R. Dahl Introduction 175 Enzyme Kinetics 176 Dosimetry of Inhalants in the Respiratory Tract 180 Respiratory-Tract Enzymes Involved in Xenobiotic Metabolism 183 Induction and Inhibition of Respiratory-Tract Xenobiotic-Metabolizing Enzymes 186 Summary 187 Acknowledgment 188 References 188 PART 4: DISPOSITION OF INHALED MATERIAL Chapter 8 Deposition and Clearance of Inhaled Particles 191 Richard B. Schlesinger Introduction 191 Deposition of Inhaled Particles 191 Clearance of Deposited Particles 203 Conclusion 216 References 217 Chapter 9 Pulmonary Retention of Particles and Fibers: Biokinetics and Effects of Exposure Concentrations 225 M. B. Snipes Introduction 225 The Pulmonary Region of the Respiratory Tract 227 viii CONTENTS Biokinetics of Particles and Fibers Deposited in the Pulmonary Region 228 Effects of Size on Biokinetics of Particles and Fibers 232 Effects of Exposure Concentrations on Lung Retention and Clearance 240 Summary 247 Acknowledgments 248 References 248 Chapter 10 Regional Dosimetry of Inhaled Reactive Gases 257 Frederick J. Miller and Julia S. Kimbell Introduction 257 Factors Influencing Absorption 259 Dosimetry Model Formulation 264 Implementing the Dosimetry Model 268 Examples of Dosimetry Models 271 Summary 281 References 282 Chapter 11 Factors Modifying the Disposition of Inhaled Organic Compounds 289 James A. Bond and Michele A. Medinsky Introduction 289 Physiochemical Factors 290 Biological Factors 299 Conclusions 312 References 313 PART 5: EVALUATION OF THE RESPOSES OF THE RESPIRATORY TRACT TO INHALED TOXICANTS Chapter 12 Carcinogenic Responses of the Lung to Inhaled Toxicants 319 Fletcher F. Hahn Introduction 319 General Principles of Lung Carcinogenesis 320 Agents Causing Tumors of the Lung 334 Summary 343 Acknowledgments 344 References 344 CONTENTS ix Chapter 13 Assessment of Pulmonary Function and the Effects of Inhaled Toxicants 355 Joe L. Mauderly Introduction 355 Role of Pulmonary Function Tests 356 Ventilation 372 Gas Distribution 391 Alveolar-Capillary Gas Exchange 395 Perfusion 401 Summary 403 Acknowledgments 404 References 404 Chapter 14 Immunologic Responses of the Respiratory Tract to Inhaled Materials 413 David E. Bice Introduction 413 Primary Immune Responses after Pulmonary Immunization 414 Secondary Immune Responses after Pulmonary Immunization 417 Immune Cells and Tissues at Risk to Inhaled Materials 418 Effects of Inhaled Materials on Pulmonary Immune Responses 420 Induction of Pulmonary Hypersensitivity by Inhaled Materials 422 Animal Models for Hypersensitivity 429 Summary 430 Acknowledgment 430 References 431 Chapter 15 Biological Markers in the Respiratory Tract 441 Rogene F. Henderson What Are Biomarkers? 442 Biomarkers of Exposure 444 Biomarkers of Effects 449 Biomarkers of Susceptibility 458 Strategies for the Use of Biomarkers 461 Summary 463 Acknowledgment 463 References 463 X CONTENTS Chapter 16 Role of Cytokines in Pulmonary Inflammation and Fibrosis 471 Kevin E. Driscoll Introduction 471 Cytokines 472 Role of Cytokines in Pulmonary Inflammation and Fibrosis 476 Cytokines as Biomarkers of Lung Toxicity 495 Conclusion 496 References 496 Chapter 17 Applications of Behavioral Measures to Inhalation Toxicology 505 Bernard Weiss and Alice Rahill Introduction 505 Measures of Aversive and Irritant Properties 506 Ozone 506 Behavioral Toxicity of Volatile Organic Solvents 5ll Inhalation as a Source of Exposure to Neurotoxic Metals 520 Chemical Sensitivity Syndromes 524 Summary 528 Acknowledgments 528 References 529 Chapter 18 Noncarcinogenic Responses of the Respiratory Tract to Inhaled Toxicants 533 Donald L. Dungworth, Fletcher F. Hahn, and Kristen J. Nikula Introduction 533 Factors Affecting Anatomic Location of Damage 534 Nose 537 Larynx 546 Acute Responses of the Lung to Inhaled Toxicants 546 Chronic Responses of the Lung to Inhaled Toxicants 550 Correlation between Acute and Chronic Responses 555 Exposure Concentration-Time-Response Relationships for Reactive Gases 559 Time-Response Relationships for Particles 563 CONTENTS xi Correlation between In Vitro and In Vivo Findings 565 Conclusions 565 References 566 PART 6: RISK ASSESSMENT Chapter 19 Risk Assessment for Inhaled Toxicants 579 Roger 0. McClellan Introduction 579 Sources of Information for Assessing Risk 583 Approaches to Risk Assessment 586 Risk Assessments for Regulated Air Pollutants 606 Summary 632 References 633 Index 639
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