A Physiologically Based Pharmacokinetic Model for Arsenic Exposure: I. Development in Hamsters and Rabbits

A physiologically based pharmacokinetic model for exposure to inorganic arsenic in hamsters and rabbits has been developed. The model in its present state simulates three routes of exposure to inorganic arsenic: oral intake, intravenous injection, and intratracheal instillation. It describes the tis...

Full description

Saved in:
Bibliographic Details
Published in:Toxicology and applied pharmacology 1996-03, Vol.137 (1), p.8-22
Main Authors: Mann, S., Droz, P.O., Vahter, M.
Format: Article
Language:English
Subjects:
Administration, Oral
Animals
Arsenic - administration & dosage
Arsenic - metabolism
Arsenic - pharmacokinetics
Biological and medical sciences
Chemical and industrial products toxicology. Toxic occupational diseases
Computer Simulation
Cricetinae
Digestive System - metabolism
Energy Metabolism
Injections, Intravenous
Intubation, Intratracheal
Lung - metabolism
Medical sciences
Metals and various inorganic compounds
Models, Biological
Rabbits
Tissue Distribution
Toxicology
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A physiologically based pharmacokinetic model for exposure to inorganic arsenic in hamsters and rabbits has been developed. The model in its present state simulates three routes of exposure to inorganic arsenic: oral intake, intravenous injection, and intratracheal instillation. It describes the tissue concentrations and the urinary and fecal excretions of the four arsenic metabolites: inorganic As(III) and As(V), methylarsonic acid, and dimethylarsinic acid. The model consists of five tissue compartments, chosen according to arsenic affinities: liver, kidneys, lungs, skin, and others. The model is based on physiological parameters, which were scaled according to body weight. When physiological parameters were not available, the data for the model were obtained by fitting (tissue affinity, absorption rate, and metabolic rate constants). The excretions of the arsenic metabolites in urine and feces are well simulated with the model for both species. Further validation of the arsenic metabolite concentrations in the tissues andin vitromeasurements of the tissue affinity constants are discussed.
ISSN:0041-008X
1096-0333
DOI:10.1006/taap.1996.0052