Vanadium pentoxide

exposed to the lowest dose (approximately 0.22 

µg/day). These results are likely to be

explained by altered pulmonary function in the higher-dose groups, resulting in lung

clearance rates that were lower than in the low-dose group. Lung clearance half-lives were

37, 59 and 61 days for the high, medium and low exposure groups, respectively, i.e. much

longer than in the 16-day study (see above). Apparently, vanadium is cleared more rapidly

from the lungs of rats exposed to vanadium pentoxide for short periods of time or at low

concentrations repeatedly for longer periods. From the deposition curves over the 542

days of the study, the estimated total vanadium lung doses were 130, 175 and 308 

µg for

the 0.5-, 1- and 2-mg/m

3

exposure groups, respectively. Normalized lung doses (

µg vana-

dium/mg vanadium pentoxide per m

3

) were not constant but decreased with increasing

exposure, i.e., 260, 175 and 154 

µg per mg/m

3

for low, medium and high dose groups,

respectively. This decrease was due to the reduced deposition of vanadium with increasing

exposure concentration. Rats retained approximately 10–15% of the estimated lung dose

on day 542. Concentrations of vanadium in blood were much lower than in lung and were

only marginally higher in exposed rats than in controls. Vanadium concentrations in blood

of exposed animals peaked on days 26 or 54, then declined throughout the rest of the

study. Because the changes were small, it was difficult to distinguish between decreased

absorption from the lung, resulting from reduced deposition, and increased elimination

from the blood (National Toxicology Program, 2002).

Kyono et al. (1999) showed that the health status of the lung influences the deposition

and retention of vanadium. In an experimental model for nickel-induced bronchiolitis in

rats, bronchiolitic rats and control animals were exposed to vanadium pentoxide

(2.2 mg/m

3

; MMAD, 1.1 

µm) for 5 h. The vanadium content in the lungs of controls was

higher (about 100%) than in bronchiolitic rats after 1 day of exposure, but 2 days later the

retention was 20% in controls and 80% in bronchiolitic rats. Elimination of vanadium was

found to be much slower in bronchiolitic rats.

(ii)

Intratracheal instillation 

Several studies have shown that after intratracheal instillation of vanadium pentoxide

in rats there was generally a rapid initial clearance of up to 50% during the first hour, a

second phase with a half-life of about 2 days and a third phase during which vanadium

remained in the lung for up to 63 days (Oberg et al., 1978; Conklin et al., 1982; Rhoads

& Sanders, 1985). 

(iii)

Oral administration 

Administration of vanadium pentoxide by gavage resulted in absorption of 2.6% of

the dose through the gastrointestinal tract 3 days after the treatment (Conklin et al., 1982).

Distribution was mainly to bone, liver, muscle, kidney, spleen and blood. Chronic

treatment with inorganic vanadium salts or organic vanadium has been shown to result in

significant accumulation in the bone, spleen and kidney (Mongold et al., 1990; Thompson

& McNeil, 1993; Yuen et al., 1993). 

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Studies with non-diabetic and streptozotocin-diabetic rats given vanadyl sulfate in

their drinking-water (0.5–1.5 mg/mL) for 1 year showed concentrations of vanadium to

be in the following order [of distribution]: bone > kidney > testis > liver > pancreas >

plasma > brain. Vanadium was found to be retained in these organs 16 weeks after cessa-

tion of treatment while the concentrations in plasma were below the limits of detection at

this time (Dai et al., 1994). 

(b)

Cellular studies

Edel and Sabbioni (1988, 1989) showed accumulation of vanadium in hepatocytes

and kidney cells (in the nucleus, cytosol and mitochondria) in rats exposed to vanadium

as radioactive 

48

V (V) pentavanadate ions and 

48

V (IV) tetravalent ions by intratracheal

instillation, oral administration or intravenous injection.

Cell cultures (human Chang liver cells, bovine kidney cells), incubated in medium

supplemented with vanadium in the form of vanadate, have been shown to accumulate

this element in the nucleus and mitochondria (Bracken et al., 1985; Stern et al., 1993; Sit

et al., 1996). In BALB/3T3 C1A31-1-1 cells incubated in the presence of sodium vana-

date and vanadyl sulfate, the cellular retention of both compounds was similar. After

exposure to a non-toxic dose (1 

µM for 48 and 72 h), nearly all vanadium was present in

the cytosol, but at a toxic dose (10 

µM for 48 and 72 h), 20% of the vanadium was found

in cellular organelles (Sabbioni et al., 1991).

4.2

Toxic effects

4.2.1

Humans

In humans, acute vanadium poisoning can manifest itself in a number of symptoms

including eye irritation and tremors of the hands (Lewis, 1959). In addition, a greenish

colouration of the tongue has been observed in humans exposed to high concentrations of

vanadium pentoxide and is probably due to the formation of trivalent and tetravalent

vanadium complexes (Wyers, 1946). The green colour disappears within 2–3 days of

cessation of exposure (Lewis, 1959).

(a)

Studies with volunteers

Zenz and Berg (1967) studied the effects of vanadium pentoxide in nine male volun-

teers exposed in an inhalation chamber to concentrations of vanadium pentoxide of 0.1,

0.25, 0.5 or 1.0 mg/m

3

(particle size, 98% < 5 

µm) for 8 h, with follow-up periods of 11–19

months. Acute respiratory irritation was reported, which subsided within 4 days after

exposure (see also Section 4.1.1).

No skin irritation was reported in 100 human volunteers after skin patch testing with

1, 2 and 10% vanadium pentoxide in petrolatum (Motolese et al., 1993).

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