A Physiologically Based Pharmacokinetic Model for Arsenic Exposure: II. Validation and Application in Humans

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,...

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Bibliographic Details
Published in:Toxicology and applied pharmacology 1996-10, Vol.140 (2), p.471-486
Main Authors: Mann, Sabine, Droz, Pierre-Olivier, Vahter, Marie
Format: Article
Language:English
Subjects:
Administration, Inhalation
Administration, Oral
Animals
Arsenates - pharmacokinetics
Arsenates - toxicity
Arsenates - urine
Arsenic - pharmacokinetics
Arsenic - toxicity
Arsenic - urine
Arsenic Poisoning
Arsenicals - pharmacokinetics
Arsenicals - urine
Arsenites - pharmacokinetics
Arsenites - toxicity
Arsenites - urine
Biological and medical sciences
Chemical and industrial products toxicology. Toxic occupational diseases
Cricetinae
Drinking - drug effects
Dust - adverse effects
Environmental Exposure - adverse effects
Environmental Exposure - statistics & numerical data
Humans
Medical sciences
Medicin och hälsovetenskap
Metals and various inorganic compounds
Models, Biological
Rabbits
Toxicology
Water - adverse effects
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Summary: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.
ISSN:0041-008X
1096-0333
DOI:10.1006/taap.1996.0244