Inhalation Toxicology

Written by internationally recognized scientists from academic, industrial, and governmental sectors, Inhalation Toxicology, Second Edition details the methods and materials used in the theoretical and applied aspects of inhalation toxicology. The editors emphasize the relationship between the respiratory system and toxicology of inhaled substances

The International Life Sciences Institute (ILSI), a nonprofit, public foundation, was established in 1978 to advance the sciences of nutrition, toxicology, and food safety. ILSI promotes the resolution of health and safety issues in these areas by sponsoring research, conferences, publications, and educational programs. Through ILSI's programs, scientists from government, academia, and industry unite their efforts to resolve issues of critical importance to the public. As part of its commitment to understanding and resolving health and safety issues, ILSI is pleased to sponsor this series of monographs that consolidates new scientific knowledge, defines research needs, and provides a background for the effective application of scientific advances in toxicology and food safety. Alex Malaspina President International Life Sciences Institute Contents Series Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi Part I. Approaches to Assessing the Toxicity of Airborne Toxicants Chapter 1. Standard-Setting as an Integrative Exercise: Alchemy, Juggling, or Science? . . . . . . . . . . . . . . . . . . . . . . . 1 D. v. Bates Chapter 2. Species Differences in Inhalation Toxicology: Variations in Exposure-Dose Relationships and Macrophage Function. . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 J. D. Brain Chapter 3. Cell Populations of the Respiratory System: Interspecies Diversity in Composition, Distribution, and Morphology . . . . . . . . . . . . . . . . . . . . . . . . 25 e. G. Plopper, A. Mir, J. St. George, N. Tyler, A. Mariassy, D. Wilson, S. Nishio, D. Cranz, J. Heidsiek, and D. Hyde Chapter 4. Comparative Metabolic Basis for the Disposition and Toxic Effects of Inhaled Materials . . . . . . . . . . . . . . . . . 41 A. R. Dahl Part II. Methodological Issues in Designing and Conducting Studies with Laboratory Animals Chapter 5. Exposure Facilities and Aerosol Generation and Characterization for Inhalation Experiments. . . . . . . . . .

This book focuses on an important aspect of the methods in laboratory animal inhalation toxicology. It is targeted to students in toxicology programs and scientists contemplating performing inhalation studies.

Recent developments have provided new data on the subject of inhalation toxicology, requiring an update of the previous edition of this popular text. Like the first, this second edition explains the basic concepts and quantitative approaches in inhalation toxicology, and it gives a comprehensive treatment of evaluations of respiratory responses to inhaled particles and gases. The author here explores new understanding of the role of cytokines in pulmonary inflammation and risk assessment. Immunologists, oncologists, respiratory specialists and students in those fields will find Concepts In Inhalation Toxicology to be essential to their practice.

The lungs provide a significant opportunity for the introduction of both therapeutic and toxic chemicals into the human body. In occupational and domestic environments, hazardous chemicals can enter the body through the lungs via gases, aerosols, and particulates from natural and anthropogenic sources. Fully updated with new research and discoveries since the last edition, Inhalation Toxicology, Third Edition presents contributions from internationally recognized scientists in the academic, commercial/industrial, and governmental sectors. A pragmatic resource for practicing professionals and students, the book comprehensively examines the relationship between the respiratory system and the toxicology of inhaled substances. Topics include: Regulatory aspects of exposure and testing Testing equipment and procedures Respiratory allergy and irritation of the respiratory tract Risk assessment Toxicology theory Toxicology modeling Toxic effects of some individual toxicants New topics in this third edition include collection and characterization of airborne particulate matter, the inhalation toxicology of asbestos fibers and nanoparticles, and the development of lung-on-a-chip technology for predicting in vivo responses. Each chapter concludes with thought-provoking questions and answers, enhancing the book’s educational utility.

This book deals with the methods and scientific basis of inhalation toxicology. It describes devices and facilities needed to expose animals to inhaled particles and gases as well as approaches to estimating or measuring the fraction of the inhaled material that is retained in the respiratory tract. The book then reviews the evergrowing repertoire of techniques that can be used to measure the responses elicited by the exposure. Quantitative and qualitative anatomical, physiological, and biochemical strategies are discussed in detail. We believe that the toxicology of inhaled materials is an important and timely topic for several'reasons. During the past decade, morbidity and mortality attributable to cardiovascular disease have significantly decreased. Progress in combatting cancer, the second most important cause of death, has been slower, and lung cancer actually became the leading cause of death in men and the second leading cause of cancer death in women. In addition, the incidence of non-neo plastic respiratory diseases such as emphysema, fibrosis, and chronic bronchitis has increased the past decade. In the United States, the National Institutes of Health (NIH) has recently reported that chronic obstructive pulmonary disease affects nearly 10 miliion persons and accounts for 59,000 deaths yearly; indeed, it ranks as the fifth leading cause of death. Because the incidence is increasing, the NIH estimates that it may become the nation's fourth or even third leading cause of death by the year 2000.

This report considers the biological and behavioral mechanisms that may underlie the pathogenicity of tobacco smoke. Many Surgeon General's reports have considered research findings on mechanisms in assessing the biological plausibility of associations observed in epidemiologic studies. Mechanisms of disease are important because they may provide plausibility, which is one of the guideline criteria for assessing evidence on causation. This report specifically reviews the evidence on the potential mechanisms by which smoking causes diseases and considers whether a mechanism is likely to be operative in the production of human disease by tobacco smoke. This evidence is relevant to understanding how smoking causes disease, to identifying those who may be particularly susceptible, and to assessing the potential risks of tobacco products.

APPROACHES TO ASSESSING THE TOXICITY OF AIRBORNE TOXICANTS; STANDARD-SETTING AS AN INTEGRATIVE EXERCISE: ALCHEMY, JUGGLING, OR SCIENCE; SPECIES DIFFERENCES IN INHALATION TOXICOLOGY: VARIATIONS IN EXPOSURE-DOSE RELATIONSHIPS AND MACROPHAGE FUNCTION; CELL POPULATIONS OF THE RESPIRATORY SYSTEM: INTERSPECIES DIVERSITY IN COMPOSITION, DISTRIBUTION AND MORPHOLOGY; COMPARATIVE METABOLIC BASIS FOR THE DISPOSITION AND TOXIC EFFECTS OF INHALED MATERIALS; METHODOLOGICAL ISSUES IN DESIGNING AND CONDUCTING STUDIES WITH LABORATORY ANIMALS; EXPOSURE FACILITIES AND AEROSOL GENERATION AND CHARACTERIZATION FOR INHALATION EXPERIMENTS; DIFFERENT METHODS USED IN ACUTE AND SUBCHRONIC INHALATION STUDIES OF POTENTIAL LUNG IRRITANTS, WITH PARTICULAR ATTENTION TO LUNG FUNCTION; CHRONIC INHALATION TOXICITY STUDIES: PROTOCOLS AND PITFALLS; CARCINOGENICITY PROTOCOLS.