Vanadium pentoxide

formation in vivo. However, high doses (over 150 

µmol/kg bw [27 mg/kg bw] had toxic

inhibitory effects (Yamaguchi et al., 1989).

(viii) Immunological effects

In the National Toxicology Program study (2002), a localized inflammatory response

was seen in the lungs of male F344/N rats and female B6C3F

1

mice exposed by inhalation

to 4, 8, or 16 mg/m

3

vanadium pentoxide in a 16-day study. Increases in cell numbers,

protein, neutrophils and lysozymes in BALF were observed but the number of macro-

phages in lavage fluids of male rats and female mice exposed to 8 or 16 mg/m

3

was

decreased. No effects were seen on systemic immunity in rats and mice. 

When weanling and adult ICR mice were given 6 mg/kg bw vanadium pentoxide by

gavage (5 days per week for 6 weeks), an increase in the number of leukocytes and plaque-

forming cells, as well as enhanced phytohaemagglutinin responsiveness, increased spleen

weight and depression of phagocytosis were observed in treated mice. In Wistar rats given

vanadium pentoxide in drinking-water (1 or 100 mg/L for 6 months), the higher dose

resulted in increased spleen weight and concanavalin-A responsiveness; a depression of

phagocytosis was found in a dose-dependent manner. These results suggest activation of T-

and B-cell immune responses (Mravcová et al., 1993).

(ix)

Biochemical effects

Chakraborty et al. (1977) gave male albino rats vanadium pentoxide orally at a dose

of 3 mg/kg bw five times a week for the first week and 4 mg/kg bw for a further 2 weeks

and found that it induced histological and enzymatic alterations including inhibition of

biosynthesis, enhanced catabolism and increased use of L-ascorbic acid in the liver and

kidney tissues of the rats.

(b)

In-vitro studies

(i)

Organ culture

Garcia  et al. (1981) found that treatment with vanadium pentoxide (10

–5

–10

–2

M

[1.82–1820 

µg/mL]) produced dose-dependent contractions of the rat vas deferens organ

cultures in vitro; a response that could be associated with the inhibition of Na

+

/K

+

-ATPase

activity. 

Schiff and Graham (1984) used organ cultures of hamster trachea to study the in-vitro

effects of vanadium pentoxide (0.1, 1, 10 or 100 

µg/mL) and oil-fired fly ash (10, 50, 100

or 250 

µg/mL) on mucociliary respiratory epithelium following exposure for 1 h per day for

9 consecutive days. Vanadium pentoxide was found to decrease ciliary activity and produce

ciliostasis in tracheal ring explants. The degree of change depended on the concentration and

length of exposure; early morphological alterations consisted of vacuolization of both nuclei

and cytoplasm of tracheal epithelium cells.

Preincubation of rat kidney brush border membrane vesicles with 1 mM [182 

µg/mL]

vanadium pentoxide for 8 h significantly inhibited citrate uptake in a time-dependent

manner. This effect was attributed to a direct interaction of vanadium with the sodium

IARC MONOGRAPHS VOLUME 86

264

pp227-292.qxp  31/05/2006  09:49  Page 264

---

citrate cotransporter. The results suggest that vanadium pentoxide has nephrotoxic poten-

tial (Sato et al., 2002).

(ii)

Cell culture

In cultures of bovine alveolar macrophages, Fisher et al. (1986) found that vanadium

pentoxide was the most cytotoxic compound when compared with other metals or

metalloids (zinc oxide, nickel sulfide, manganese oxide, sodium arsenite, sodium selenite)

tested. Vanadium caused a reduction in phagocytosis by macrophages to 50% of control

values after incubation for 20 h at a concentration of 0.3 

µg/mL, but this concentration was

also associated with a substantial (59%) loss of macrophage viability. The authors con-

cluded that their results confirmed those of previous studies (Waters et al., 1974) which

demonstrated that vanadium is a unique macrophage toxicant.

Vanadium(V) and related compounds are known to exert potent toxic effects on a

wide variety of biological systems. One of the pathways of vanadium(V) toxicity is

thought to be mediated by oxygen-derived free radicals (Zychlinski et al., 1991; Shi et al.,

1997; Ding et al., 1999).

Parfett and Pilon (1995) evaluated the effects of promoters such as vanadium com-

pounds on oxidative stress-regulated gene expression and promotion of morphological

transformation in C3H/10T1/2 cells. Promoters which elevate intracellular oxidant levels

can be distinguished by a spectrum of induced gene expression which includes the oxi-

dant-responsive murine proliferin gene family. Proliferin transcription was found to be

induced 20-fold by 5 

µM [0.9 µg/mL] vanadium pentoxide. Another pentavalent vana-

dium, ammonium metavanadate (5 

µM [0.6 µg/mL]), added as promoter in two-stage

morphological transformation assays, amplified yields of Type II and Type III foci in

monolayers of 20-methylcholanthrene-initiated C3H/10T1/2 cells. These results suggest

that pentavalent vanadium compounds could promote morphological transformation in

these cells by creating a cellular state of oxidative stress, which induces the expression of

proliferin. Proliferation of MCF-7 cells was found to be stimulated after 4-day treatments

with 0.5–2 

µM vanadium(V); the effect reached a plateau at 1 µM vanadium, declined at

3 

µM and disappeared at 5 µM (Auricchio et al., 1995; 1996).

To determine the effect of vanadium pentoxide on the release of two major immuno-

regulatory cytokines, mouse macrophage-like WEHI-3 cells were treated in vitro (Cohen

et al., 1993). Vanadium pentoxide decreased the release of IL-1 and TNF

α stimulated

with lipopolysaccharide endotoxin. Spontaneous release of the IL-1/TNF-regulating pros-

tanoid prostaglandin E

2

(PGE

2

) was significantly increased by the highest concentration

of ammonium metavanadate tested, although lipopolysaccharide endotoxin-stimulated

PGE

2

production was unaffected. These results showed that pentavalent vanadium could

alter the host’s immunocompetence. In another study with WEHI-3 cells treated with

100

µM or 100 nM vanadium pentoxide or ammonium metavanadate, the capacity of

macrophage-like cells to bind and respond to interferon 

γ was altered (Cohen et al., 1996). 

When mice and rat hepatocytes or human Hep G2 cells were treated in vitro with

vanadium pentoxide (1, 10 or 100 

µM), gene expression (after 2-h treatment) and

VANADIUM PENTOXIDE

265

pp227-292.qxp  31/05/2006  09:49  Page 265

---