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Comparison of tissue dosimetry in the mouse following chronic exposure to arsenic compounds

Gentry, P. Robinan, Covington, Tammie R., Lawrence, Greg, McDonald, Tracy, Snow, Elizabeth T., Germolee, Dori, Moser, Glenda, Yager, Janice W. and Clewell, Harvey J. III 2005, Comparison of tissue dosimetry in the mouse following chronic exposure to arsenic compounds, Journal of toxicology and environmental health. Part A, vol. 68, no. 5, pp. 329-351, doi: 10.1080/15287390590900813.

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Title Comparison of tissue dosimetry in the mouse following chronic exposure to arsenic compounds
Author(s) Gentry, P. Robinan
Covington, Tammie R.
Lawrence, Greg
McDonald, Tracy
Snow, Elizabeth T.
Germolee, Dori
Moser, Glenda
Yager, Janice W.
Clewell, Harvey J. III
Journal name Journal of toxicology and environmental health. Part A
Volume number 68
Issue number 5
Start page 329
End page 351
Publisher Taylor and Francis Inc.
Place of publication Abingdon, England
Publication date 2005-01
ISSN 1528-7394
1087-2620
Keyword(s) environmental & ecological toxicology
environmental health
Summary Several chronic bioassays have been conducted in multiple strains of mice in which various concentrations of arsenate or arsenite were administered in the drinking water without a tumorigenic effect. However, one study (Ng et al., 1999) reported a significant increase in tumor incidence in C57Bl/6J mice exposed to arsenic in their drinking water throughout their lifetime, with no tumors reported in controls. A physiologically based pharmacokinetic model for arsenic in the mouse has previously been developed (Gentry et al., 2004) to investigate potential differences in tissue dosimetry of arsenic species across various strains of mice. Initial results indicated no significant differences in blood, liver, or urine dosimetry in B6C3F1 and C57Bl/6 mice for acute or subchronic exposure. The current work was conducted to compare model-predicted estimates of tissue dosimetry to additional kinetic information from the (C57Bl/6 x CBA)F1 and TgAc mouse. The results from the current modeling indicate that the pharmacokinetic parameters derived based on information in the B6C3F1 mouse adequately describe the measured concentrations in the blood/plasma, liver, and urine of both the (C57Bl/6 x CBA)F1 and TgAc mouse, providing further support that the differences in response observed in the chronic bioassays are not related to strain-specific differences in pharmacokinetics. One significant finding was that no increases in skin or lung concentrations of arsenic species in the (C57Bl/6 x CBA)F1 strain were observed following administration of low concentrations (0.2 or 2 mg/L) of arsenate in the drinking water, even though differences in response in the skin were reported. These data suggest that pharmacodynamic changes may be observed following exposure to arsenic compounds without an observable change in tissue dosimetry. These results provided further indirect support for the existence of inducible arsenic efflux in these tissues.
Language eng
DOI 10.1080/15287390590900813
Field of Research 111506 Toxicology (incl Clinical Toxicology)
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2005, Taylor & Francis
Persistent URL http://hdl.handle.net/10536/DRO/DU:30008877

Document type: Journal Article
Collection: School of Biological and Chemical Sciences
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