Vanadium pentoxide

with 0.88, 3.0 or 13.0 mg/kg bw vanadium pentoxide for 4 weeks induced pathological

lung lesions that developed dose-dependently, and were characterized by exudative

inflammation, injury of alveolar macrophages, and swelling and mucous degeneration of

the broncho-bronchiolar epithelium.

(iii)

Hepatic effects

In mice exposed to vanadium pentoxide (0.02 M inhaled for 30 min), fatty degene-

ration, extramedullary haematopoietic activity and neutrophilic infiltration around the

central veins were detected in the liver (Acevedo-Nava et al., 2001; abstract only).

In rats and rabbits, fatty changes with necrosis in the liver and a drastic reduction in liver

tissue respiration have been observed as a result of long-term exposure to vanadium pen-

toxide by inhalation (10–70 mg/m

3

, 2 h per day, 9–12 months) (Roshchin, 1968, cited by

Lagerkvist, 1986). Livers and kidneys of rats treated with vanadium(V) showed an electron

paramagnetic resonance signal characteristic of vanadium(IV) (Johnson et al., 1974).

The bioenergetic functions of liver mitochondria have been studied in vivo and in vitro

following acute and chronic exposure of rats to vanadium pentoxide via the respiratory

tract or exposure of isolated rat liver mitochondria to various vanadium pentoxide concen-

trations.  In vivo, the mitochondrial respiration with glutamate (as nicotinamide adenine

dinucleotide (NAD)-linked substrate) or succinate (as flavine adenine dinucleotide

(FAD)-linked substrate) was inhibited significantly when compared with control animals.

No inhibition was found with ascorbate as cytochrome c-linked substrate. The same

effects were observed in vitro. These combined effects provide evidence that vana-

dium(V) acts as an inhibitor of respiration in rat liver mitochondria. It was postulated that

significant amounts of vanadium(V) accumulated in the intermembrane space of liver

mitochondria of exposed rats. The enzymatic process of detoxification, by reduction of

vanadium(V) in the tissue, may be insufficient to prevent the deleterious action of this

compound on liver mitochondria (Zychlinski & Byczkowski 1990).

(iv)

Renal effects

Glomerular hyperaemia and necrosis of convoluted tubules in the kidney were observed

in some early studies of acute toxicity of vanadium compounds in various mammalian

species (Hudson, 1964; Pazhynich, 1966; WHO, 1988). 

Intraperitoneal administration of sodium orthovanadate to rats resulted in inhibition of

tubular reabsorption of sodium and hypokalaemic distal renal tubular acidosis with

increased urinary pH (Bräunlich et al., 1989; Dafnis et al., 1992). Vanadium, in the form

of ammonium metavanadate injected subcutaneously into rats, was found to be toxic to the

kidney at doses of 0.6 and 0.9 mg/kg bw per day for 16 days. Histological changes were

observed, including necrosis, cell proliferation and fibrosis. Vanadium was shown to be

more toxic for the kidneys in rats when given by a parenteral route (Al-Bayati et al., 1989).

Chronic treatment of rats with vanadyl sulfate has been shown to result in significant

accumulation of the element in the kidneys (Mongold et al., 1990; Thompson & McNeill,

1993); however, most is probably bound to small peptides or macromolecules in the form

IARC MONOGRAPHS VOLUME 86

262

pp227-292.qxp  31/05/2006  09:49  Page 262

---

of vanadyl and thus is not available as vanadate, a more potent inhibitor of Na

+

/K

+

-

ATPases (Cantley et al., 1977; Rehder, 1991; Thompson et al., 1998).

(v)

Nervous system effects

Neurophysiological effects have been reported following acute exposure (by oral

administration and subcutaneous injection) of dogs and rabbits to vanadium oxides and

salts (vanadium trioxide, vanadium pentoxide, vanadium trichloride and ammonium meta-

vanadate). These effects included disturbances of the central nervous system, such as

impaired conditioned reflexes and neuromuscular excitability (Roshchin, 1967a). The

animals behaved passively, refusing to eat, and lost weight. In cases of severe poisoning,

diarrhoea, paralysis of the hind limbs and respiratory failure were followed by death

(Hudson, 1964; Roshchin, 1967b, 1968).

In a study reported by Seljankina (1961 cited by Lagerkvist et al., 1986 and WHO,

1988), solutions of vanadium pentoxide were administered orally to rats and mice at doses

of 0.005–1 mg/kg bw per day for periods ranging from 21 days at the higher concen-

trations to 6 months at the lower concentrations. A dose of 0.05 mg/kg bw was found to

be the threshold dose for functional disturbances in conditioned reflex activity in both

mice and rats. Repeated exposure to aqueous solutions (0.05–0.5 mg/kg bw per day, for

80 days) of vanadium pentoxide impaired conditioned reflex mechanisms in rats. 

In male CD-1 mice exposed by inhalation to 0.02 M vanadium pentoxide 2 h twice a

week for 4 weeks, Golgi staining revealed a drastic reduction in dendritic spines in the

striatum compared with controls, showing that the inhalation of vanadium causes severe

neuronal damage in the corpus striatum (Montiel-Flores et al., 2003; abstract only). Using

the same inhalation model, after 12 weeks of exposure, a decrease in dendritic spines of

granule cells of the olfactory bulb was observed (Mondragón et al., 2003; abstract only).

In addition, ultrastructural modifications in nuclear morphology of these cells were evi-

dent, Golgi apparatus was dilated and an increase in lipofucsin granules was observed, as

well as necrosis of some cells (Colin-Barenque et al., 2003; abstract only). In the cere-

bellum, necrosis and apoptosis of the Purkinje and granule cell layers were seen (Meza

et al., 2003; abstract only).

(vi)

Cardiovascular system effects

Perivascular swelling, as well as fatty changes in the myocardium, were observed by

Roshchin (1968, cited by WHO, 1988) following chronic exposure of rats and rabbits to

vanadium pentoxide (10–70 mg/m

3

, 2 h per day, 9–12 months) by inhalation. 

(vii) Skeletal alterations

The effect of vanadium pentoxide on bone metabolism has been investigated in

weanling rats. Vanadium pentoxide (10.0–200.0 

µmol/kg bw [1.8–36.4 mg/kg bw]) was

administered orally for 3 days. Low doses (10–100 

µmol/kg bw [1.8–18 mg/kg bw])

caused increases in alkaline phosphatase activity and DNA content in the femoral

diaphysis, indicating that vanadium pentoxide may play a role in the enhancement of bone

VANADIUM PENTOXIDE

263

pp227-292.qxp  31/05/2006  09:49  Page 263

---