Physiologically based pharmacokinetic modeling of arsenic in the mouse

Détails

ID Serval
serval:BIB_813FF7E7084A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Physiologically based pharmacokinetic modeling of arsenic in the mouse
Périodique
Journal of Toxicology and Environmental Health. Part A
Auteur(s)
Gentry P. Robinan , Covington Tammie R., Mann Sabine, Shipp Annette M., Yager Janice W., Clewell Harvey J.
ISSN
1528-7394
Statut éditorial
Publié
Date de publication
2004
Peer-reviewed
Oui
Volume
67
Numéro
1
Pages
43-71
Langue
anglais
Notes
SAPHIRID:49689
Résumé
A remarkable feature of the carcinogenicity of inorganic arsenic is that while human exposures to high concentrations of inorganic arsenic in drinking water are associated with increases in skin, lung, and bladder cancer, inorganic arsenic has not typically caused tumors in standard laboratory animal test protocols. Inorganic arsenic administered for periods of up to 2 yr to various strains of laboratory mice, including the Swiss CD-1, Swiss CR:NIH(S), C57Bl/6p53(+/-), and C57Bl/6p53(+/+), has not resulted in significant increases in tumor incidence. However, Ng et al. (1999) have reported a 40% tumor incidence in C57Bl/6J mice exposed to arsenic in their drinking water throughout their lifetime, with no tumors reported in controls. In order to investigate the potential role of tissue dosimetry in differential susceptibility to arsenic carcinogenicity, a physiologically based pharmacokinetic (PBPK) model for inorganic arsenic in the rat, hamster, monkey, and human (Mann et al., 1996a, 1996b) was extended to describe the kinetics in the mouse. The PBPK model was parameterized in the mouse using published data from acute exposures of B6C3F1 mice to arsenate, arsenite, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) and validated using data from acute exposures of C57Black mice. Predictions of the acute model were then compared with data from chronic exposures. There was no evidence of changes in the apparent volume of distribution or in the tissue-plasma concentration ratios between acute and chronic exposure that might support the possibility of inducible arsenite efflux. The PBPK model was also used to project tissue dosimetry in the C57Bl/6J study, in comparison with tissue levels in studies having shorter duration but higher arsenic treatment concentrations. The model evaluation indicates that pharmacokinetic factors do not provide an explanation for the difference in outcomes across the various mouse bioassays. Other possible explanations may relate to strain-specific differences, or to the different durations of dosing in each of the mouse studies, given the evidence that inorganic arsenic is likely to be active in the later stages of the carcinogenic process. [Authors]
Pubmed
Web of science
Création de la notice
12/05/2009 13:43
Dernière modification de la notice
03/03/2018 18:47
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