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

Abstract

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 (approximately 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.

Vanadium pentoxide inhalation

“…There may be a pathological pattern within the lung which may be associated with the pattern and/or extent of vanadium deposition. [40] Its cumulative effect in lung tissue possibly contributes to the development lung cancer. Indeed, in lung tissue excised from post-mortem investigations, the mean vanadium concentrations of 1.36 ± 0.08 (sd) (1990s) were higher than 1.04 ± 0.05 in the 1960s.…”

“…[9] Vanadium lung exposure studies in rats appear to reach a steady state in low exposure groups of 0.5 mg/m 3 . [10] The retention rate of vanadium in rats aged 18 months was 13-15%. [10]…”

First Steps Towards an Understanding of a Mode of Carcinogenic Action for Vanadium Pentoxide

“…These kinetic studies were reported to show that the lung burdens of vanadium appeared to reach steady-state with time at the lowest administered concentrations (0.5 mg/m 3 for rats and 1 mg/m 3 for mice), but at higher concentrations the lung burdens in both species declined with time after reaching maximum values at about 6 months for rats and 1–2 months for mice. The tabulated data in Dill et al (2004) also suggest that, if the only determinant for lung tumours was the lung burden of vanadium (µg V/g lung) then one might predict the tumour incidences in female rats exposed to 1 or 2 mg/m 3 to be very similar to the incidences in female mice exposed to the same atmospheric concentrations of vanadium pentoxide 27 . This is because the lung burdens at these concentrations in the two species were very similar throughout the exposure period, with eight measurements taken, beginning on day 1 and ending on day 535.…”

Computational modeling of nanoscale and microscale particle deposition, retention and dosimetry in the mouse respiratory tract

“…Fewer datasets on deposition and clearance of particles in the respiratory tract of mice are available than for other species (Dill et al, 2004, Kuehl et al, 2012, Oberdorster and Finkelstein, 1995, Raabe et al, 1988). Menache et al (1995) developed particle-size dependent, inhalability curves for humans and a group of small animals based on measurements of particle deposition in the respiratory tract.…”