title: Establishing aerosol exposure concentrations for inhalation toxicity studies.
abstract: Criteria for the selection of aerosol concentrations to be used in inhalation studies assessing the toxicity and carcinogenicity of chemical substances were discussed by the authors in a meeting sponsored by the National Toxicology Program. Concepts in the design of aerosol inhalation studies emerged from that meeting and are being communicated through this publication. Inhalation studies assessing the toxicity and carcinogenicity of aerosols have often used maximum exposure levels on the basis of technological feasibility. Evidence has now accumulated that the amount of pulmonary burden of deposited particles impacts on particle clearance above some as yet not well-defined exposure concentration. The sequelae are such that lung clearance decreases with increased particulate burden to the point of approaching complete cessation. 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 retention. The subject matter of this paper is a rapidly developing area in terms of knowledge. Accordingly, the contents of this article are intended as guidelines and not as absolute rules for the conduct and interpretation of inhalation exposure studies.
authors.affiliation: Division of Biomedical and Behavioral Science, National Institute for Occupational Safety and Health, Cincinnati, Ohio 452276.
authors.forename: T R
authors.initials: TR
authors.lastname: Lewis
authors.forename: P E
authors.initials: PE
authors.lastname: Morrow
authors.forename: R O
authors.initials: RO
authors.lastname: McClellan
authors.forename: O G
authors.initials: OG
authors.lastname: Raabe
authors.forename: G L
authors.initials: GL
authors.lastname: Kennedy
authors.forename: B A
authors.initials: BA
authors.lastname: Schwetz
authors.forename: T J
authors.initials: TJ
authors.lastname: Goehl
authors.forename: J H
authors.initials: JH
authors.lastname: Roycroft
authors.forename: R S
authors.initials: RS
authors.lastname: Chhabra
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001822:Body Burden; D004391:Dust; D008168:Lung / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000336:Aerosols; D004391:Dust