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

• Published in: Toxicological sciences Vol. 77; no. 1; pp. 6 - 18
• Main Authors: Dill, Jeffrey A., Lee, Kyeonghee M., Mellinger, Kathleen H., Bates, Derrick J., Burka, Leo T., Roycroft, Joseph H.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.01.2004
• Subjects: Administration, Inhalation; Animals; chronic inhalation; clearance; Dose-Response Relationship, Drug; Female; Lung - drug effects; Lung - metabolism; Lung - pathology; lung deposition; Mice; Mice, Inbred Strains; Models, Biological; Organ Size - drug effects; Rats; Rats, Inbred F344; Toxicity Tests, Chronic; toxicokinetics; vanadium; Vanadium Compounds - administration & dosage; Vanadium Compounds - pharmacokinetics; Vanadium Compounds - toxicity; vanadium pentoxide; vanadium pentoxide (V2O5)
• DOI: 10.1093/toxsci/kfh005
• ISSN: 1096-6080; 1096-0929

Female F344 rats and B6C3F1 mice were exposed to vanadium pentoxide (V2O5) at concentrations of 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 after 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 vs. 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 in 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 with rats (13–15% 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 decreases 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.