Improvements in Modeling of Pulmonary Uptake of Toxicants.
Abstract
The primary objective of this technical report is to provide a rational foundation for quantitatively evaluating the importance of unsteady versus steady or quasi-steady events during uptake of chemical toxicants via the human respiratory tract. A secondary objective is to review critically the current approaches in physiologically-based pharmacokinetic (PBPK) modeling of the lung with a view to generalizing the model descriptions to encompass a broader range of exposure and physiological conditions. The secondary objective is addressed frist, with a succinct review of the transport mechanisms that con operate within the respiratory tract when exposed to a concentration of chemical toxicants in the form of vapors, aerosols, and particulate matter. Functional relationships are reviewed within the context of a voluminous body of international literature bearing on this and related subjects of importance. Computational models are proposed to provide an essential complementary research tool with not only simulative but also predictive capabilities. Drawing upon this considerable background of established knowledge, one can proceed more readily with a detailed study of the very important question posed as the primary objective; namely, the establishment of an order-of- magnitude analysis resulting in a general classification scheme that identifies three major flow regimes, distinguished on the basis of whether the flow is dominated by unsteadiness, viscous effects, or the effects of convective acceleration. The report concludes with some important recommendations regarding the extrapolation of test results performed on small laboratory animals to the human context.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 1994
- Accession Number
- ADA299030
Entities
People
- R. Collins