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Comparison of Tissue Dosimetry in the Mouse Following Chronic Exposure to Arsenic Compounds

Citation

Gentry, PR and Covington, TR and Lawrence, G and McDonald, T and Snow, ET and Germolec, D and Yager, JW and Clewell, HJ, Comparison of Tissue Dosimetry in the Mouse Following Chronic Exposure to Arsenic Compounds, Journal of Toxicology and Environmental Health. Part A, 68, (5) pp. 329-351. ISSN 1528-7394 (2005) [Refereed Article]

DOI: doi:10.1080/15287390590900813

Abstract

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 × 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 × 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 × 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.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Pharmacology and Pharmaceutical Sciences
Research Field:Toxicology (incl. Clinical Toxicology)
Objective Division:Health
Objective Group:Public Health (excl. Specific Population Health)
Objective Field:Environmental Health
Author:Snow, ET (Associate Professor Elizabeth Snow)
ID Code:44629
Year Published:2005
Web of Science® Times Cited:6
Deposited By:Health Sciences A
Deposited On:2007-06-13
Last Modified:2007-06-13
Downloads:0

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