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I I I i I I I I I I I I I I I I I I AUTHOFI; Lewis, Trent R., Aoul E. Morrow, Roger O. McClellan, Otto G. Raabe, Gerald L. Kennedy, Bernard A. Schwetz, Thomas J. Goehl, Joseph H. Roycroft, and Rajendra S. Chhabra DATE:1989 .'r.~: ESTABLISHING AEROSOL EXPOSURE CONCENTRATIONS FOR INHALATION TOXICITY STUDIES. ~ITATION: TOXICOLOGY AND APPLIED PHARMACOLOGY 99, 377-383 (1989) STUDY DESIGN= Criteria for the selection of aerosol concentrations to be used in inhalation studies assessing the toxicity and carcinogenicity of chemical substances were discussed by authors in a meeting sponsored by the National Toxicology Program. Concepts in the design of aerosol inhalation studies which emerged from that meeting are communicated in this publication. This paper focuses on the major determinants in establishing maximal aerosol concentrations for use in inhalation toxicity studies with special emphasis on experimental design features to assess lung retentlon. RNDING$/RESULTS= The key point that is made is that all toxicity studies conducted with inhaled particulate material must involve a determination of the actual amount of test material in the lung as a function of time. The measurement of lung burden is appropriate at all exposure levels at 3,6,12, 18,24 and 30 months after initiation of exposure in a chronic bioassay. Temporal determinations of lung aerosol retention must be incorporated into the prechronic studies to adequately plan a chronic btoassay. Another key point was the importance of biologic differences which distinguish establishing maximum aerosol concentrations in inhalation studies from maximum tolerated doses using the oral and parenteral means of administering varying amount of a test chemical to experimental subjects. This paper attempted to highlight the importance of understanding the relationships among exposure concentrations and durations, the particle size and species dependency of fractional deposition of an aerosol in various regions of the respiratory tract, dose (lung burden), and toxicologic response as they' relate to inhalation toxicity studies.