Vanadium pentoxide

(Kanematsu & Kada, 1978; Kanematsu et al., 1980). However, vanadium pentoxide was

not mutagenic in several strains of E. coli or S. typhimurium. But Si et al. (1982) (cited

by Sun et al., 1996) demonstrated that vanadium pentoxide induced reverse mutations in

E. coli WP2, WP2uvrA and CM-981, but not frameshift mutations in strains ND-160 or

MR102. This compound showed negative results in S. typhimurium strains TA100,

TA1535, TA1537, TA1538, TA97, and TA98. 

Bis(cyclopentadienyl)vanadium chloride (1 to 33 

µg/plate) was mutagenic or weakly

mutagenic in strains TA97 and TA100 without exogenous metabolic activation system, but

not mutagenic in strains TA1535 and TA98 with or without metabolic activation (Zeiger

et al., 1992).

In another series of studies, vanadium pentoxide (0.33 to 333.00 

µg/plate) was not

mutagenic in S. typhimurium strains TA97, TA98, TA100, TA102 or TA1535, with or

without induced rat or hamster liver S9 enzymes (National Toxicology Program, 2002).

No increase in the frequency of micronucleated normochromatic erythrocytes was

seen in peripheral blood samples from male or female B6C3F

1

mice exposed to vanadium

pentoxide by inhalation in concentrations up to 16 mg/m

3

for 3 months. Furthermore, no

effect was seen in the ratio of polychromatic erythrocytes/normochromatic erythrocytes

in peripheral blood, indicating a lack of toxicity to the bone marrow by vanadium

pentoxide (National Toxicology Program, 2002). 

[The Working Group was aware of positive results on induction of mitotic recombi-

nation by vanadium pentoxide in Drosophila; the data were reported in BSc and MSc

theses].

In Chinese hamster lung fibroblast cell lines, vanadium pentoxide induced endo-

reduplication and micronuclei which were shown to be kinetochore-positive, but did not

induce gene mutation nor sister chromatid exchange.

In human lymphocytes cultured in vitro, positive genotoxic effects of vanadium

pentoxide were demonstrated for the induction of DNA damage with the alkaline ‘Comet

Assay’ (two studies from the same laboratory), sister chromatid exchange when the com-

pound was given in combination with caffeine (one study out of three), chromosomes

associated, satellite associations and polyploidy with Hoechst staining (a single study),

aneuploidy with fluorescence in-situ hybridization staining and inhibition of microtubule

polymerization with immunostaining (a single study).

Vanadium pentoxide was shown to inhibit repair of double-strand breaks induced in

human fibroblasts by UV radiation or bleomycin in both the neutral and alkaline comet

assays.

(ii)

In-vivo studies

In CD-1 mice, induction of DNA damage by vanadium pentoxide administered intra-

peritoneally was demonstrated with the alkaline ‘Comet Assay’ in several organs. In the

same mouse strain, a lack of sister chromatid exchange and chromosomal aberrations was

reported in bone marrow; however, dominant lethal effects were observed after intraperi-

toneal injection of vanadium pentoxide (8.5 mg/kg bw).

VANADIUM PENTOXIDE

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In 615 and Kunming albino mice, micronuclei were induced in bone marrow by vana-

dium pentoxide administered by inhalation, by subcutaneous injection or by intraperi-

toneal injection. The results were negative following oral administration. Micronuclei

were also seen in fetal liver after intraperitoneal injection of vanadium pentoxide into

pregnant mice. No induction of dominant lethals was observed.

A single in-vivo study of the induction of chromosomal aberrations in albino rats was

inconclusive (number of animals not reported).

(c)

Genetic changes in vanadium pentoxide-induced tumours

In a National Toxicology Program study (2002), male and female B6C3F

1

mice were

exposed by inhalation to 1, 2, or 4 mg/m

3

vanadium pentoxide for 2 years (see

Section 3.1.1). The lung carcinomas that developed as a result of this exposure showed a

high frequency of K-Ras mutation, loss of heterozygosity in the region of the K-Ras gene

on chromosome 6 and activation of MAP kinase (Zhang et al., 2001b; Devereux et al., 2002;

National Toxicology Program, 2002). The authors concluded that these genetic alterations

played an important role in vanadium pentoxide-induced lung carcinogenesis. On the other

hand, there was no evidence of overexpression of mutant p53 suggesting no evidence of a

role for altered p53 function in the lung carcinomas due to exposure to vanadium pentoxide

(Devereux et al., 2002; National Toxicology Program, 2002).

4.5

Mechanistic considerations

Vanadium pentoxide is considered to induce oxidative damage leading to DNA alkali-

labile sites and DNA strand breakage.

Inhibition of microtubule polymerization may explain the aneugenic effects of vana-

dium pentoxide. Whether these spindle disturbances are related to oxidative damage or to

direct interaction with vanadium cations is unclear. Indirect effects of vanadium pentoxide

through inhibition of various enzymes involved in DNA synthesis and DNA repair also

contribute to its genotoxicity.

Induction of dominant lethal mutations in mice may result from one, or a combi-

nation, of the modes of action mentioned above.

5.

Summary of Data Reported and Evaluation

5.1

Exposure data

Vanadium is widely distributed in the earth’s crust in a wide range of minerals and in

fossil fuels. Vanadium pentoxide, the major commercial product of vanadium, is mainly

used in the production of alloys with iron and aluminium. It is also used as an oxidation

catalyst in the chemical industry and in a variety of minor applications. Exposure to vana-

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