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ToxSci Advance Access published online on November 4, 2003
Toxicological Sciences, doi:10.1093/toxsci/kfh005
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
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Received August 6, 2003; accepted September 25, 2003
© 2003 Society of Toxicology

Biotransformation and Toxicokinetics

Lung Deposition and Clearance of Inhaled Vanadium Pentoxide in Chronically Exposed F344 Rats and B6C3F1 Mice

Jeffrey A. Dill 1*, Kyeonghee M. Lee 1, Kathleen H. Mellinger 1, Derrick J. Bates 1, Leo T. Burka 2, and Joseph H. Roycroft 2

1 Battelle, Toxicology Northwest, Richland, WA 99352
2 National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709

* To whom correspondence should be addressed. E-mail: dillj{at}battelle.org.


  Abstract

Female F344 rats and B6C3F1 mice were exposed to vanadium pentoxide (V2O5) at 0, 0.5, 1, or 2 mg/m3 (rats) and 0, 1, 2, or 4 mg/m3 (mice) for 6 h/day, 5 days/week for up to 18 months by whole-body inhalation. Lung weights and lung burdens of vanadium were determined for exposed animals after 1, 5, and 12 days, and 1, 2, 6, 12, and 18 months of V2O5 exposure. Blood vanadium concentrations were determined at 1, 2, 6, 12, and 18 months for all animals including controls. A model that assumed a first-order deposition rate and a first-order elimination rate for vanadium was employed to fit the lung burden data. Comparisons between exposed groups indicated a progressive increase in lung weight with exposure concentration and time on exposure for both species. The vanadium lung burdens appeared to reach steady-state in the lowest exposure groups (0.5 and 1 mg/m3 for rats and mice, respectively) but showed a decline in the higher exposure groups. This deposition pattern was similar between rats and mice but the maximum lung burdens were observed at different times (1 or 2 months in mice versus 6 months in rats). The vanadium deposition rate decreased faster in mice, while the elimination half-lives of vanadium lung burdens were about six- to nine-fold shorter in mice than those of rats at 1 and 2 mg/m3. Thus, the retention of vanadium in the lungs at 18 months was lower in mice (~2% retained) compared to rats (13 to 15% retained) at the common exposure concentrations of 1 and 2 mg/m3. The lung burden data were approximately proportional to the exposure concentration in both species, likely due to concomitant decrease in deposition and elimination to a similar extent with increasing exposure. The area under the lung burden versus time curves and the area under the blood concentration (control-normalized) versus time curves were also proportional to exposure concentration. The progression of pathological changes in the lung with exposure and time is thought to affect the pattern and/or extent of vanadium deposition in the lungs following repeated exposures to V2O5.

Key Words: vanadium, vanadium pentoxide (V2O5), lung deposition, clearance, chronic inhalation, toxicokinetics .


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