1. Aerosols and Gases

• Introduction
• The Impact of Aerosols
• Size Regimes
• Aerosol Terminology
• Direct Observation of Aerosol Particles
• Cigarette Smoke: A Familiar Aerosol System
• Particle Size
• Size Distributions
• Aerosol Properties
• Shape
• Density
• Electrical Charge
• Mechanisms of Charging
• Attraction of a Charged Particle to a Nearby Conductor
• Charge Distributions
• Decay Rate of Charges on Particles
• Light Scattering
• Hygroscopicity
• Surface Area
• Aerosol Dynamics
• Particle Motion
• Gravitational and Buoyant Forces
• The Resistance or Drag Force
• Terminal Settling Velocities
• Slip, or Cunningham’s Correction
• Brownian Motion
• Coagulation
• Particle Size and Toxicity
• Particle Mass
• Aerodynamic Properties
• Surface Area
• Other Size-Dependent Factors
• Properties of Gases
• Movement from Air into Tissues
• Expressing Concentration
• Solubility

2. The Respiratory Tract

• Introduction
• Postnatal Development
• Compartments
• Gross Anatomy
• Overview
• Nose, Nasopharynx, and Larynx
• Tracheobronchial Tree
• Trachea
• Bronchi and Bronchioles
• Respiratory Bronchioles
• Parenchyma or Pulmonary Region
• Subgross Lung Types
• Cells and Tissues
• Ciliated Mucosa
• The Alveolus
• The Macrophage
• Mucus-Secreting Glands
• Innervation of the Respiratory System
• Bronchial Musculature
• Ventilation
• Normal Breathing
• Exercise
• Reflex Responses to Inhaled Irritants
• Deposition of Inhaled Particles
• Introduction
• Aerosol Deposition Models
• Uptake of Inhaled Gases
• Defenses
• Introduction
• Proximal Airways’ Clearance Mechanisms
• Mucociliary Clearance
• Alveolar Clearance

3. Establishing and Controlling Exposures

• Introduction
• Cleaning and Conditioning Throughput Air
• Contaminants in Supply Air
• Gas Cleaning
• Removal of Water Vapor
• Removal of Unwanted Pollutant Gases
• Removal of Unwanted Particles
• Air Purification and Conditioning Systems
• Aerosol Generation
• General Considerations
• Monodisperse Aerosols
• Polydisperse Aerosols
• Droplet Generators
• Dry Dust Generators
• Gas Generation
• General Considerations
• Common Techniques
• Compressed Gas Cylinders
• Syringe Injectors
• Vaporization and Sublimation Systems
• Permeation Tubes
• Chemical and Physical Reactions
• Mixed Aerosols and Gases
• Principles for Stabilizing The Exposure Atmosphere
• Generator Stability
• Exposure System Stability
• Real-Time Adjustments

4. Characterizing Exposures

• Introduction
• The Breathing Zone
• What Should Be Measured?
• Particle Parameters
• Gas Parameters
• Environmental Parameters
• Instrumentation for Aerosol Characterization
• Comment
• Sampling
• Size Analyzers
• Isokinetic Sampling
• Instrumentation for Gas Characterization
• Eliminating Measurement Interferences
• General Principles
• Gas/Vapor Denuders
• Sampling Protocols

5. Methods for Exposing Subjects

• Introduction
• Basic Types of Exposure Systems
• Chamber Systems
• Head-Only Exposure Systems
• Nose- or Mouth-Only Exposure Systems
• Lung and Partial Lung Exposure Systems
• Intratracheal Instillation
• Aging the Atmosphere
• Ammonia as a Contaminant
• Determination of the Inhaled Dose
• Ethical Responsibilities of the Investigators

6. Testing for Toxicity

• Introduction
• Quantitation
• Anatomical Considerations
• Respiratory Tract Regions and Common Diseases
• Extrathoracic (Head) Airways
• Tracheobronchial Airways
• Pulmonary (Gas Exchange) Airways
• Morphologic Evaluations
• Morphometry
• Pulmonary Function
• Other Endpoints
• Pulmonary Defense
• Lung Development
• Behavior
• Biochemical
• Normal Lung Biochemistry
• Lung Lavage
• Detoxification, Activation
• Extrapulmonary Responses
• Controls
• Batteries Of Endpoints

7. Experimental Designs

• Introduction
• Basic Statistical Considerations
• Two Types of Statistics
• Type 1 and Type 2 Errors in Hypothesis Testing
• Some Tests of Significance
• Group Size
• The Role of the Statistician
• Examples of Common Designs
• Acute Exposures/Dose–Response Relationships
• Repeated Exposures/Dose Fractionation
• Chronic Exposures/Carcinogenesis, Mutagenesis, and Teratogenesis
• Chronic Exposures
• Carcinogenicity
• Mutagenicity
• Teratogenicity
• Multicomponent Atmospheres

8. Facilities and Support Considerations

• Introduction
• Facilities Components
• Laboratory Buildings
• Exposure Systems
• Animal Housing
• Necropsy
• Data Handling
• Analytical Support
• Toxicity Testing
• Shop Support
• Conference, Library, and Office Space
• Facilities Location

9. Animal Models

• Introduction
• General Considerations
• Models of Human Diseases
• Extrapolation from Laboratory Animals to Humans
• Comparative Dose Distribution
• Dose and Dose Variability
• Comparative Minute Ventilation per Unit Body Mass
• Comparative Physiology and Anatomy
• Comparative Pulmonary Function
• Comparative Airway Anatomy
• Common Laboratory Animal Models
• Dogs
• Ferrets
• Nonhuman Primates
• Horses
• Bovids
• Rodents
• Other Mammals

10. Regulations and Guidelines

• Introduction
• Guidelines versus Regulations
• Protection of Laboratory Personnel
• Protection of Research Subjects
• Human Subjects
• Laboratory Animal Subjects
• Inhalation Toxicity Testing Guidelines

• Robert F. Phalen, University of California at Irvine, Irvine, California, USA
  Robert Phalen co-directs the Air Pollution Health Effects Laboratory at the University of California, Irvine (UCI). He also holds two academic appointments in the College of Health Sciences at UCI: Professor in the Department of Community and Environmental Medicine; and Professor in the Department of Medicine’s Center for Occupational and Environmental Health. He has served as Chair of both the UCI Institutional Review Board (for Human Studies) and the Institutional Animal Care and Use Committee. He is currently a member of the United States Environmental Protection Agency’s Clean Air Scientific Advisory Committee—Particulate Material, and he is a member of 11 professional scientific associations/societies.
  
  In 1971, he obtained a Ph.D. in biophysics, with specialization in inhalation toxicology, from the University of Rochester (in Rochester, NY). His postdoctoral research was conducted at the Inhalation Toxicology Research Institute (now the Lovelace Respiratory Research Institute) in Albuquerque, NM. In 1972, Dr. Phalen joined the then College of Medicine at UCI to establish the Air Pollution Health Effects Laboratory, which still conducts studies relating to the toxicology of air pollutants, and trains graduate students and physicians in inhalation toxicology.
  
  His research is in several areas including: predicting doses from inhaled particles; health effects of inhaled air pollutants; and applied aerosol physics. He has published over 100 scientific papers, and authored and/or edited four previous books on aerosol inhalation topics.