A physiologically based pharmacokinetic model for arsenic exposure. II. Validation and application in humans

Details

Serval ID
serval:BIB_5254
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A physiologically based pharmacokinetic model for arsenic exposure. II. Validation and application in humans
Journal
Toxicology and Applied Pharmacology
Author(s)
Mann S., Droz P.O., Vahter M.
ISSN
0041-008X
Publication state
Published
Issued date
1996
Peer-reviewed
Oui
Volume
140
Number
2
Pages
471-486
Language
english
Abstract
A physiologically based pharmacokinetic model (PB-PK) for inorganic arsenic exposure in humans has been developed. This model is an extension of a PB-PK model for hamsters and rabbits, with adjustments for body weight, metabolic rates, and absorption rates. It describes the absorption, distribution, metabolism, and excretion of arsenate, arsenite (As(III)), methyl arsonate, and dimethyl arsinate, the four major metabolites of inorganic arsenic. The routes of intake considered are inhalation of arsenic dust and fumes and oral intake of arsenic via drinking water and food. The PB-PK model for the oral exposure route is validated using data on urinary excretion after repeated oral exposure to As(III) as well as after exposure to inorganic As via drinking water. Absorption by inhalation is validated using data on urinary excretion after occupational exposure to arsenic trioxide dust and fumes. In both cases, the model gives satisfactory results for urinary excretion of the four As metabolites. The PB-PK model is also used in the description of the effects on the kinetics of exposure via different routes and for the simulation of various realistic exposure scenarios.
Keywords
Administration, Inhalation, Administration, Oral, Animals, Arsenates/pharmacokinetics, Arsenates/toxicity, Arsenic/pharmacokinetics, Arsenic/toxicity, Arsenic Poisoning, Arsenicals/pharmacokinetics, Arsenicals/urine, Arsenites/pharmacokinetics, Arsenites/toxicity, Cricetinae, Drinking/drug effects, Dust/adverse effects, Environmental Exposure/adverse effects, Environmental Exposure/statistics & numerical data, Humans, Models, Biological, Rabbits, Water/adverse effects
Pubmed
Web of science
Create date
19/11/2007 12:41
Last modification date
20/08/2019 14:07
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