The International Life Sciences Institute (ILSI) was estab lished in 1978 to stimulate and support scientific research and educational programs related to nutrition, toxicology, and food safety, and to encourage cooperation in these programs among scientists in universities, industry, and government agencies to assist in the resolution of health and safety issues. To supplement and enhance these efforts, ILSI has made a major commitment to supporting programs to harmon ize toxicological testing, to advance a more uniform inter pretation of bioassay results worldwide, to promote a common understanding of lesion classifications, and to encourage wide discussion of these topics among scien tists. The Monographs on the Pathology of Laboratory Ani mals are designed to facilitate communication among those involved in the safety testing of foods, drugs, and chemicals. The complete set will cover all organ systems and is intended for use by pathologists, toxicologists, and others concerned with evaluating toxicity and carcinogen icity studies. The international nature of the project - as reflected in the composition of the editorial board and the diversity of the authors and editors - strengthens our ex pectations that understanding and cooperation will be im proved worldwide through the series. Alex Malaspina President International Life Sciences Institute Preface This book, on the nervous system, is the sixth volume of a set pre pared under the sponsorship of the International Life Sciences Insti tute (ILSI)."

The International Life Sciences Institute (ILSI) was creat ed to promote cooperative efforts toward solving critical health and safety questions involving foods, drugs, cosmet ics, chemicals, and other aspects of the environment. The Officers and Trustees believe that questions regarding health and safety are best resolved when government and industry rely on scientific investigations, analyses, and re views by independent experts. Further, the scientific aspects of an issue should be examined and discussed on an international basis, separate from the political concerns of individual companies. ILSI is pleased to sponsor this set of monographs on the pathology of laboratory animals. This project will be use ful in improving the scientific basis for the application of pathologic techniques to health and safety evaluation of substances in our environment. The world wide distribu tion of the authors, editors, and Editorial Board who are creating these monographs strengthens the expectation that international communication and cooperation will al so be strengthened."

The International Life Sciences Institute (ILSI) was estab lished to stimulate and support scientific research and edu cational programs in nutrition, toxicology, and food safe ty; and to encourage cooperation in these programs among scientists from universities, industry, and government in order to facilitate the resolution of health and safety issues. The officers and trustees of ILSI believe that questions re garding health and safety are best resolved when govern ment and industry rely on scientific investigations, analy ses, and reviews by independent experts. This process is furthered by the examination and discussion of issues on an international basis. ILSI is pleased to sponsor this set of monographs on the pathology of laboratory animals. This project collectively brings together the most comprehensive information on non-neoplastic and neoplastic lesions that occur in com monly used laboratory animals. The international compo sition of the authors, editors, and editorial board who have contributed to these monographs strengthens our expecta tions that understanding and cooperation will be strength ened worldwide through this series."

The International Life Sciences Institute (ILSI) was creat ed to promote cooperative efforts toward solving critical health and safety questions involving foods, drugs, cosmet ics, chemicals, and other aspects of the environment. The Officers and Trustees believe that questions regarding health and safety are best resolved when government and industry rely on scientific investigations, analyses, and reviews by independent experts. Further, the scientific aspects of an issue should be examined and discussed on an international basis, separate from the political concerns of individual companies. ILSI is pleased to sponsor this set of monographs on the pathology of laboratory animals. This project will be use ful in improving the scientific basis for the application of pathologic techniques to health and safety evaluation of substances in our environment. The world wide distribu tion of the authors, editors, and Editorial Board who are creating these monographs strengthens the expectation that international communication and cooperation will al so be strengthened."

The International Life Sciences Institute (ILSI) was estab lished to stimulate and support scientific research and edu cational programs in nutrition, toxicology, and food safe ty; and to encourage cooperation in these programs among scientists from universities, industry, and government in order to facilitate the resolution of health and safety issues. The officers and trustees of ILSI believe that questions re garding health and safety are best resolved when govern ment and industry rely on scientific investigations, analy ses, and reviews by independent experts. This process is furthered by the examination and discussion of issues on an international basis. ILSI is pleased to sponsor this set of monographs on the pathology of laboratory animals. This project collectively brings together the most comprehensive information on non-neoplastic and neoplastic lesions that occur in com monly used laboratory animals. The international compo sition of the authors, editors, and editorial board who have contributed to these monographs strengthens our expecta tions that understanding and cooperation will be strength ened worldwide through this series."

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. . . . . . . . . .

Scientists from both academia and industry in many countries have closely cooperated to arrive at a consensus on the descriptions of all the types of tumour and preneoplastic lesions encountered in laboratory mice. The series of fascicles should provide information and guidelines especially adapted for international use in practical toxicologic pathology. Images showing the typical appearance of the discussed lesions and references to the most recently published papers complete the information presented here.

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 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . xiii . . . . . . . . . . . . . Part I. Integrative Approach to Assessing Human Health Risk: Two Contemporary Problems Chapter 1. Integrating Diverse Data Sets to Assess the Risks of Airborne Pollutants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 R.o. McClellan, R.G. Cuddihy, w.e. Griffith, and J. L. Mauderly Chapter 2. Risk Assessment for Radon Inhalation Based on Animal Exposure Data and Human Epidemiology . . . . . . . 23 . F. Steinhausler Part II. Types of Evidence: General Strengths and Weaknesses Section 1. Epidemiological Chapter 3. Inhalation Hazards: The Interpretation of Epidemiologic Evidence. . . . . . . . . . . . . . . . . . . . 39 . . . . . . . J.e. Bailar Chapter 4. Problems in Interpreting Epidemiological Data 49 P.N. Lee Section 2. Animal Chapter 5. Rodent Carcinogenicity Studies: Their Value and Limitations. . . . . . . . . . . . . . . . . . . . . . . . . . 61 . . . . . . . . . .

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.

During the years that have intervened since the third volume of the International Life Seiences Institute (ILSI) Monographs on Pathology of Laboratory Animals, Digestive System, was published, new information of interest to pathologists has developed at a rather remarkable pace. Standardized nomenclature has been proposed and gained significant acceptance during the period since the first edition and isbeing utilized on aninternational basis. Thishas resulted in improvement in communi cationof pathologic data to reguiatory agencies and inscientific publica tions worldwide. This monograph series and others sponsored by ILSI have had significant effects on improved communications and the inter national acceptance of standardized nomenclature. In this second edition, new formats have been used in some instances where more appropriate for the subjects to be eovered. The format introduced in the first edition remains useful as it emphasizes the neces sityto reeognize the morphologie features of pathologic lesions to iden tify them precisely. This identifieation is an essential first step toward development of new insightsintopathogenetic meehanismsand their use in decisions eventually applieable to public health. Newinformation is included in thisedition on the nature and variability of preneoplastic lesions in the Iiver of laboratory rodents. Data on the aeeompanying changes in enzyme activity in affeeted Iiver cells are ex panded, and additional information on spongiosis hepatis in the rat and its relation to spongiotic pericytoma is a further feature. In a few in stanees, research on a pathologie entity has been Iimitedbut its recogni tionremains important. Thisjustifiesinclusion of suchentities in the new edition."