Accession Number : ADA138847

Title :   Modeling of Inhalation Administration of Vapors with Capacity Limited Clearance.

Descriptive Note : Final scientific rept. 30 Jun 81-31 Aug 83,


Personal Author(s) : Thomas,V

PDF Url : ADA138847

Report Date : 31 Aug 1983

Pagination or Media Count : 100

Abstract : The overall objective of the project was to design economical and informative testing of subacute and chronic toxicity of new volatile substances. The specific objectives were: (1) to prepare a mathematical model for simulation of uptake, distribution, and elimination of vapors with capacity-limited clearance; (2) to obtain experimental data supporting the model; (3) to study the factors affecting nonlinearity of clearance (concentration dependence, interference of inhalation of other vapors). The main accomplishments are: (1) A program for mathematical solution of a multi-compartmental model for simulation of uptake, distribution, and elimination of vapors having a capacity limited elimination pathway was prepared for the Apple II Plus computer and tested by simulating a variety of trichloroethylene and halothane exposures. (2) Three methods for determination of metabolic clearance were tested: (a) systemic clearance was determined from the concentration differences in inhaled air and arterial blood; (b) intrinsic clearance in organs was determined from distribution of inhaled chemicals in the body during steady state; (c) intrinsic clearance by each metabolic pathway was determined from distribution and elimination of metabolites. (3) The retention of vapors of water soluble chemicals in trachea was determined and the significance of retention of chemicals in respiratory airways is discussed.

Descriptors :   *Inhalation, *Toxicity, *Mathematical models, *Vapors, Metabolism, Simulation, Computerized simulation, Metabolites, Tissues(Biology), Rats

Subject Categories : Toxicology

Distribution Statement : APPROVED FOR PUBLIC RELEASE