Vanadium pentoxide

and lung of rats were noted at all doses, and rats exposed to 

≥ 4 mg/m

3

developed fibrosis

(National Toxicology Program, 2002).

In addition, decreases in heart rate and in diastolic, systolic and mean blood pressure

were seen in male and female F344/N rats exposed to 16 mg/m

3

. These effects were not

attributed to a direct cardiotoxic action of vanadium pentoxide but were considered to

reflect the poor condition of the animals coupled with an effect of the anaesthesia (used

to facilitate implantation of electrodes for electrocardiogram measurements). The overall

pulmonary changes indicated the presence of restrictive lung disease in both sexes

exposed to vanadium pentoxide concentrations of 

≥ 4 mg/m

3

, while an obstructive lung

disease may have been present in the group exposed to 16 mg/m

3

(National Toxicology

Program, 2002).

In a two-year study, F344/N rats and B6C3F

1

mice (50 animals per sex and per species)

were exposed to vanadium pentoxide at concentrations of 0, 0.5, 1 or 2 (rats only), 1, 2 or 4

(mice only) mg/m

3

, by inhalation for 2 years. Non-neoplastic proliferative and inflammatory

lesions of the respiratory tract were observed in both species at increasing frequency with

increased exposure concentration (see Tables 3.1.1 and 3.1.2, Section 3) (National

Toxicology Program, 2002; Ress et al. 2003). The main differences observed between acute

(3 months) and chronic (2 years) effects of exposure to vanadium pentoxide were the deve-

lopment by 2 years of chronic inflammation of the bronchi, septic bronchopneumonia, inter-

stitial infiltration and proliferation, and emphysema (National Toxicology Program, 2002). 

When rabbits were exposed to vanadium pentoxide by inhalation (8–18 mg/m

3

, 2 h per

day, 9–12 months) and rats to vanadium pentoxide condensation aerosol (3–5 mg/m

3

, 2 h

per day every 2 days, 3 months) or vanadium pentoxide dust (10–40 mg/m

3

, 4 months),

similar respiratory effects (sneezing, nasal discharge, dyspnoea and tachypnea) were pro-

duced in both species, which in some cases included attacks of bronchial asthma and a

haemorrhagic inflammatory process (Roshchin, 1967b, 1968, cited by WHO, 1988).

In studies carried out by Sjöberg (1950), rabbits exposed to vanadium pentoxide dust

(205 mg/m

3

) developed tracheitis, pulmonary oedema and bronchopneumonia and died

within 7 h. In another experiment, repeated inhalation of vanadium pentoxide (20–

40 mg/m

3

, 1 h per day, for several months) by rabbits produced chronic rhinitis and

tracheitis, emphysema, patches of lung atelectasis and bronchopneumonia.

When adult male cynomolgus monkeys were exposed by inhalation to 0.5 or

5.0 mg/m

3

vanadium pentoxide dust aerosol for 1 week, significant air flow limitation was

produced only at the 5.0 mg/m

3

dose in both central and peripheral airways, without

changes in parenchymal function. However, analysis of BALF showed a significant

increase in the absolute number and relative percentage of polymorphonuclear leukocytes,

indicating that vanadium pentoxide induced pulmonary inflammatory effects (Knecht

et al., 1985). In a study conducted to evaluate changes in pulmonary reactivity resulting

from repeated vanadium pentoxide inhalation through the use of provocation challenges,

and after different subchronic exposure regimens, one group of monkeys (n = 8) was

exposed by inhalation (6 h per day, 5 days per week, for 26 weeks) to 0.1 mg/m

3

vanadium

pentoxide on Mondays, Wednesdays and Fridays, with a twice-weekly peak exposure of

IARC MONOGRAPHS VOLUME 86

260

pp227-292.qxp  31/05/2006  09:49  Page 260

---

1.1 mg/m

3

on Tuesdays and Thursdays, and another group (n = 8) was exposed to a

constant daily concentration of 0.5 mg/m

3

; a control group (n = 8) received filtered, con-

ditioned air. Pre-exposure challenges with vanadium pentoxide induced airway obstruc-

tion with a significant influx of inflammatory cells into the lung in both subchronic expo-

sure groups. Inhalation of vanadium pentoxide with intermittent high exposure concen-

trations did not produce an increase in pulmonary reactivity to vanadium pentoxide, and

cytological, immunological and skin test results indicated the absence of allergic sensi-

tization (Knecht et al., 1992).

Intratracheal exposure

Zychlinski et al. (1991) investigated the toxic effects of vanadium pentoxide in rats

exposed intratracheally to 0.56 mg vanadium pentoxide/kg bw once a month for

12 months. Body weight gain of exposed animals slowed following the 10th treatment

when compared with control animals. Lung weights were significantly greater than in

controls, but other organ weights were unchanged. The glucose concentrations in blood

of treated animals were slightly decreased whereas total cholesterol concentrations were

reduced markedly. In parallel to this in-vivo study, in-vitro experiments with isolated

untreated rat lung microsomes and mitochondria in the presence of reduced nicotinamide

adenine dinucleotide phosphate (NADPH) were performed to investigate the mechanism

of the chronic toxic effects of vanadium. The results showed that vanadium(V) undergoes

one-electron redox cycling (enzymatic reduction) in rat lung biomembranes and that non-

enzymatic reoxidation of vanadium(IV) initiates lipid peroxidation under aerobic condi-

tions. It was postulated that free-radical redox cycling of vanadium may be responsible

for the observed pulmonary toxicity.

When female CD rats were instilled intratracheally with 42 or 420 

µg/kg bw vanadium

pentoxide and followed from 1 h to 10 days, pulmonary inflammation was induced in a

dose-dependent manner, but neutrophil influx was not detected until 24 h after exposure.

Expression of mRNA for two cytokines, macrophage inflammatory protein-2 (MIP-2) and

KC protein was also detected in the bronchoalveolar macrophages (Pierce et al., 1996).

Bonner et al. (2000) reported that two weeks after a single intratracheal instillation of

1 mg/kg bw vanadium pentoxide, male Sprague-Dawley rats developed constrictive air-

way pathology including airway smooth muscle cell thickening, mucous cell metaplasia

and fibrosis. 

Evaluating the effects of a single intratracheal dose of residual oil fly ash in rats, Dreher

et al. (1997), Kodavanti et al. (1998) and Silbajoris et al. (2000) concluded that vanadium

compounds were the major toxic component inducing pulmonary injury, activation of

alveolar macrophages and inflammatory changes. In addition, Silbajoris et al. (2000)

described the induction of some mitogen-activated protein (MAP) kinases in the alveolar

epithelium of the animals.

Rice  et al. (1999) instilled Sprague-Dawley rats intratracheally with 1 mg/kg bw

vanadium pentoxide and found proliferation of myofibroblasts, indicating pulmonary

fibrosis. Toya et al. (2001), using the same model, found that intratracheal instillation

VANADIUM PENTOXIDE

261

pp227-292.qxp  31/05/2006  09:49  Page 261

---