Vanadium pentoxide

the lungs and the intestine. It was not detected in heart, aorta, brain, kidney, ovary or testes,

although detection methods were reported to be insensitive (Schroeder et al., 1963; Ryan

et al., 1999).

Using AAS, Fortoul et al. (2002) analysed vanadium concentrations in lung tissue

samples from autopsies of Mexico city residents in the 1960s and 1990s (n = 39 and 48,

respectively). Vanadium concentrations were 1.04 

± 0.05 µg/g in lung samples from the

1960s and 1.36 

± 0.08 µg/g in samples from the 1990s, indicating an increase in ambient

exposure to vanadium.

4.1.2

Experimental systems

(a)

In-vivo studies

Absorption of vanadium compounds after oral administration is known to be strongly

affected by such dietary components as type of carbohydrate, fibre protein concentration,

other trace elements, chelating agents and electrolytes (Nielsen, 1987). Associated patho-

logy or physiological state may also affect vanadium absorption and hence may render a

consistent determination of a lethal dose (e.g. LD

50

) by the oral route very difficult

(Thompson et al., 1998).

In general, the absorption, distribution and elimination of vanadium pentoxide and other

vanadium compounds are similar. There are, however, variations depending on the solubility

of the administered compound, the route of exposure and the form of vanadium adminis-

tered (National Toxicology Program, 2002). 

(i)

Inhalation studies

Mice

In a National Toxicology Program tissue burden study (2002), male and female

B6C3F

1

mice were exposed to 1, 2, or 4 mg/m

3

vanadium pentoxide by inhalation for 104

weeks (for details, see Section 3.1.1). Tissue burden analyses were performed on days 1,

5, 12, 26, 54, 171, 362 and 535 after the start of treatment. Lung weights increased

throughout the study, most markedly in the group exposed to the highest concentration.

The mean lung weights of the two lower-dose groups were similar. Lung vanadium

burden increased roughly in proportion to the exposure concentration, with strong indi-

cations of linear toxicokinetics. As with the rats (see below), lung burdens in the mice did

not reach a steady state in the groups exposed to 2 and 4 mg/m

3

; they peaked near day 54

(at 5.9 and 11.3 

µg, respectively), and then declined until day 535. In the low-dose group

(1 mg/m

3

), the lung burden reached a steady state around day 26 at a level of 3 

µg vana-

dium. The same toxicokinetic model could be applied to both mice and rats (see below),

with an initial deposition rate increasing with increasing exposure concentration, and a

decline in deposition rate over the course of the study. In the group exposed to 4 mg/m

3

,

the deposition rate decreased from 0.62 to 0.27 

µg/day between day 1 and day 535 and in

the group exposed to 2 mg/m

3

it decreased from 0.41 to 0.22 

µg/day. However, in the

group exposed to the lowest dose there was a minimal decline in deposition rate between

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days 1 and 535 (0.31 to 0.26 

µg/day). Lung clearance half-lives in mice were 6, 11 and

14 days for the 1, 2 and 4 mg/m

3

exposure groups, respectively. Total vanadium lung

doses were estimated to have been 153, 162 and 225 

µg, respectively, while normalized

lung doses were 153, 80.9 and 56.2 

µg vanadium per mg vanadium pentoxide per m

3

exposure. On day 535, mice had retained approximately 2–3% of the total estimated lung

doses (National Toxicology Program, 2002). 

In an inhalation model described by Sánchez et al. (2003; abstract only), male CD-1

mice were exposed to an aerosol of 0.02 M vanadium pentoxide for 2 h twice a week for

4 weeks. Concentrations of vanadium (determined by AAS) in lung, liver, kidney, testes

and brain increased after the first week of inhalation in all the organs examined and

remained at almost the same values at the end of the fourth week. The organ with the

highest concentrations of vanadium was the liver followed by the kidney. The lowest con-

centrations were found in testes. However, at the fourth week, a decrease in concen-

trations of vanadium was observed in the kidney. 

Rats

In a study undertaken by the National Toxicology Program (2002), blood and lung

concentrations, lung clearance half-life of vanadium, and the onset and extent of vana-

dium pentoxide-induced lung injury were determined in female Fischer 344 rats exposed

to 0, 1 or 2 mg/m

3

vanadium pentoxide for 16 days. Lung weights of exposed rats were

significantly greater than those of control animals on days 0, 1 and 4 post-exposure but

were similar on day 8 post-exposure. There was little difference in lung weights between

exposed groups. AUC analysis showed that lung burdens were proportional to exposure

concentration throughout the recovery period. The results suggested linear toxicokinetics.

Lung clearance half-lives during the 8-day recovery period were similar among exposed

groups (range, 4.42–4.96 days). Concentrations of vanadium in blood were similar among

exposed groups, but several orders of magnitude lower than the concentrations in lung

tissue, and showed only marginal increases with increasing exposure doses.

In the 2-year inhalation study (National Toxicology Program, 2002), tissue burden

analyses were performed on female Fischer 344 rats on days 1, 5, 12, 26, 54, 173, 360 and

540 after the start of exposure to 0.5, 1 or 2 mg/m

3

vanadium pentoxide. Lung weights

increased throughout the study, with similar increases in the two lower-dose groups.

When lung burden data were integrated over all time points, they did appear to be

approximately proportional to exposure concentrations. During the two years, lung

burdens in the two higher-dose groups (1 and 2 mg/m

3

) did not reach a steady state, but

showed an increase until day 173 followed by a decline until day 542. In contrast, the lung

burden in the group exposed to 0.5 mg/m

3

increased with time and reached a steady state

at 173 days. The data fitted a model in which the rate of deposition of vanadium in the

lung decreased with time, while the initial deposition rates increased with the exposure

concentration. Between days 1 and 542, the calculated deposition rate decreased from

0.41 to 0.25 

µg/day in the 1-mg/m

3

exposure group and from 0.68 to 0.48 

µg/day in the

2-mg/m

3

exposure group. There was no such change in deposition rate in the group

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