Inhalation Studies

This significantly updated and expanded new edition presents the scientific foundations of inhalation research essential to the design and conduct of toxicologic studies. It incorporates the major advances that have been made in the field, including recent advances in biology and the rapidly increasing global concerns and studies on particulate air pollution. The Second Edition was motivated by: new developments in the ultrafine particle health effects and concentrated aerosol research advances in understanding postnatal lung growth and the deposition and clearance of inhaled particles new techniques in toxicity testing the explosion of knowledge in the genetic and molecular realms the introduction of a large number of transgenic animal models updated ethical guidelines for animal testing the emergence of aerosol medicine the growing threat of aerosol-related terrorism increased appreciation of nonpulmonary effects of inhaled substances use of medical scanning techniques to study respiratory tract structure the introduction of new inhalation exposure systems the emergence of aerosol concentrators for use in air pollution studies

The U.S. Environmental Protection Agency (EPA) has a mission and regulatory responsibility to protect human health and the environment. EPA's pursuit of that goal includes a variety of research activities involving human subjects, such as epidemiologic studies and surveys. Those research activities also involve studies of individuals who volunteer to be exposed to air pollutants intentionally in controlled laboratory settings so that measurements can be made of transient and reversible biomarker or physiologic responses to those exposures that can indicate pathways of toxicity and mechanisms of air-pollution responses. The results of those controlled human inhalation exposure (CHIE) studies, also referred to as human clinical studies or human challenge studies, are used to inform policy decisions and help establish or revise standards to protect public health and improve air quality. Controlled Human Inhalation-Exposure Studies at EPA addresses scientific issues and provides guidance on the conduct of CHIE studies. This report assesses the utility of CHIE studies to inform and reduce uncertainties in setting air-pollution standards to protect public health and assess whether continuation of such studies is warranted. It also evaluates the potential health risks to test subjects who participated in recent studies of air pollutants at EPA's clinical research facility.

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. . . . . . . . . .

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.

Advances in Controlled Clinical Inhalation Studies represents scientific work presented at the 3rd International Inhalation Symposium held 1991 in Hannover, FRG. The symposium covered the new developments in this field of research. The main pollutants of interest were acid aerosols, fog, and indoor pollutants, while with regard to biological effects, an emphasis was placed on immunotoxicological and biochemical parameters. Tests on high risk groups were also considered. Initial chapters describe the outdoor environment as well as indoor air, measurement and quality - both at home and in the workplace. Besides methods for clinical inhalation and assessing personal exposure, new methodologies are particularly presented. Further chapters focus on the relevance of clinical data for regulatory decisions.

1. Aerosol and gases; 2. Basic morphology and physiology of the respiratory tract; 3. Establishing and controlling exposure environments; 4. Characterizing the exposure; 5. Methods for exposure animals.

This book presents WHO guidelines for the protection of public health from risks due to a number of chemicals commonly present in indoor air. The substances considered in this review, i.e. benzene, carbon monoxide, formaldehyde, naphthalene, nitrogen dioxide, polycyclic aromatic hydrocarbons (especially benzo[a]pyrene), radon, trichloroethylene and tetrachloroethylene, have indoor sources, are known in respect of their hazardousness to health and are often found indoors in concentrations of health concern. The guidelines are targeted at public health professionals involved in preventing health risks of environmental exposures, as well as specialists and authorities involved in the design and use of buildings, indoor materials and products. They provide a scientific basis for legally enforceable standards.