This SERCA proposal is the first stage of a program focussed on the relationships between fiber size and toxicity for asbestos and other durable mineral fibers. So far, the difficulties of interpreting results from experimental animal and in vitro studies of responses to fiber exposures have been due, in part, to the wide spread ranges of diameter and length of the administered fibers. The first objective of this study is to develop techniques for generating relatively monodisperse fibrous aerosols for laboratory use. Fibrous aerosols, with diameter in a range of 0.1 to 3.0 microm and length in a range of 2.5 to 20 microm, will be generated. A fluidized bed fibrous generator will generate fibrous aerosols with number concentrations of 10(2)-10(3)/ml at an output flowrate of 10 lpm. The polydisperse fibrous aerosols will then be classified by an inertial impactor-virtial impactor-membrane filter system. We expect that the geometric standard deviations for both fiber diameter and length of a variety of specific fractions will be within 1.50. The diameter ranges of interest for subsequent biological effects testing will be 0.15, 0.3-0.5 and 2.0-3.0 microm, and the selected length ranges will be <2.5, 2.5-5.0, 5.0-10,0 and >20.0 microm. The collected fibers could be used directly in vitro, in vivo instillation, or in vivo implantation studies, or could be resuspended (with some losses) for inhalation studies. Alternatively, the aerosols passing a given length cut could be fed directly into inhalation exposure chambers for studies of differential toxicity, e.g., the differences n response from cell culture or animal population to another could be attributed to the additional presence of a longer length fraction. Such studies, made feasible by may research in the next three years, will be performed at this Institute in collaboration with colleagues having appropriate expertise in inhalation toxicology, molecular biology, and pulmonary pathology. The second current objective is to use numerical computation to explore the aerodynamic properties and filtration characteristics of fibrous particles. The theoretical results will be compared with the plentiful data from the experimental part of this project. The increased understanding of the fiber deposition behavior due to the elongated geometry will help to establish improved predictive models for lung deposition of fibers, as well as a basis for optimizing the performance of the generation system.
