Validation and Application of Pharmacokinetic Models for Interspecies Extrapolations in Toxicity Risk Assessments of Volatile Organics
Abstract
In pursuit of the goal of establishing a scientific basis for the interspecies extrapolation of pharmacokinetic data in health risk assessments, a series of studies have been conducted involving pharmacokinetic determinations in rats to several aliphatic halocarbons (with parallel studies initiated in the dog). Direct measurements of the uptake and elimination of halocarbon in rats have been completed during the following inhalation exposures and following oral administration of dichloroethylene (DCE) and perchloroethylene (PCE). An assay for the measurement of halocarbons in the tissues of exposed animals has been successfully developed, and tissue concentration profiles in the liver, kidney, lung, fat, brain, muscle, and heart have been completed for oral and intraarterial administrations of PCE. The utility of the physiologically-based pharmacokinetic model for the accurate computer simulations of the pharmacokinetics of three halocarbons with wide variation in physicochemical properties (TRI, TCE, and PCE) has been demonstrated. Keywords: Physiologically- based pharmacokinetic model; Saturable metabolism; Respiratory elimination; Halocarbon inhalation exposure; Halocarbon oral exposure; Interspecies extrapolations; Pharmacokinetics.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 21, 1989
- Accession Number
- ADA211270
Entities
People
- Cham E. Dallas
- James Gallo
- James V. Bruckner
- Raghupathy Ramanathan
- Srinivasa Muralidhara
Organizations
- University of Georgia