Vanadium pentoxide

distinct diagnoses, the lesions were considered to be one pathogenic process. The authors

concluded that this hyperplastic change was striking and appeared more prominent than

had been observed in other National Toxicology Program inhalation studies. Although the

exact pathogenesis was not determined in this study, the hyperplasia of the alveolar and

bronchiolar epithelium was consistent with bronchiolization, a process in which

bronchiolar epithelium proliferates and migrates down into alveolar ducts and adjacent

alveoli. Although there was clearly proliferation, it was thought primarily to represent a

metaplastic change. Whether this represented a precursor lesion for development of

pulmonary neoplasms is not known. The lung tumour response in rats and mice following

exposure to vanadium pentoxide was not concentration-related; there was a flat dose

response. Several dose metrics and lung-burden data were used to aid in interpretation of

lung pathology in exposed rats and mice. In the case of all dose metrics, rats received

more vanadium than mice. In mice, the total ‘dose’ was similar in the groups exposed to

1 mg/m

3

and 2 mg/m

3

and this may help explain the flat dose response in the lung neo-

plasms in male and female mice. The total dose does not explain the differences in neo-

plasms in rats compared with mice. However, when the total dose is corrected for body

weight, mice received a three- to five-fold higher dose of vanadium than rats at compa-

rable exposure concentrations of 1 and 2 mg/m

3

. Therefore, on a body weight basis, mice

received considerably more vanadium than rats, and this may help explain the differences

in responses between the species (National Toxicology Program, 2002; Ress et al., 2003).

4.

Other Data Relevant to an Evaluation of Carcinogenicity

and its Mechanisms

4.1

Deposition, retention, clearance and metabolism

Vanadium pentoxide (V

2

O

5

) is a poorly soluble oxide which, in water or body fluids,

releases some vanadium ions which may speciate either in cationic (VO

2

+

) or anionic

(HVO

4

2–

) forms [at physiological pH: H

2

VO

4

–

]. 

Toya et al. (2001) showed that vanadium pentoxide powder (geometric mean diameter,

0.31 

µm) was eight times more soluble in an artificial biological fluid (Gamble’s solution)

than in water. 

Elimination from the lung, and distribution to and elimination from tissues, is partly

a function of solubility. Sodium vanadate is more soluble than vanadium pentoxide and is

consequently cleared more rapidly from the lung (Sharma et al., 1987).

Vanadium (V) is reduced to vanadium (IV) in humans and other mammals. It is

considered to be an essential element in chickens, rats and probably humans (Nielsen,

1991; French & Jones, 1993; Crans et al., 1998; Hamel, 1998; National Toxicology

Program, 2002). The main source of vanadium intake for the general human population is

food (see also Section 1.3.5).

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4.1.1

Humans

Zenz and Berg (1967) studied responses in nine human volunteers exposed to

0.2 mg/m

3

vanadium pentoxide (particle size, 98% < 5

µm) for 8 h in a controlled environ-

mental chamber. The highest concentration of vanadium was found in the urine (0.13 mg/L

[2.6 

µM/L]) 3 days after exposure; none of the volunteers had detectable concentrations

1 week after exposure.

Pistelli et al. (1991) studied 11 vanadium pentoxide-exposed workers 40–60 h after

they had removed ashes from boilers of an oil-fired power station. Seven of the workers

were smokers compared with eight of 14 controls. Vanadium concentrations in urine were

determined by AAS and ranged between 1.4 and 27 

µg/L in the exposed group. Four of

the controls had detectable concentrations of vanadium in the urine (range, 0.5–1.0 

µg/L).

Hauser et al. (1998) determined concentrations of vanadium by means of GF-AAS in

the urine of workers overhauling an oil-fired boiler where concentrations of vanadium

pentoxide in the air ranged from 0.36 to 32.2 

µg/m

3

(mean, 19.1 

µg/m

3

). On the first day

of work on the overhaul, the mean vanadium concentrations in urine were 0.87 mg/g crea-

tinine before a shift and 1.53 mg/g creatinine after a shift. However, the vanadium con-

centrations in the start-of-shift urine samples on the last Monday of the study were not

significantly different from the start-of-shift concentrations on the previous Saturday, a

time interval of about 38 h between the end of exposure and sample collection. Spearman

rank correlation between start-of-shift concentration of vanadium in urine and concen-

tration of vanadium in workplace dust during the previous day was not strong (r = 0.35)

due to incomplete and insufficient information on respirator usage as noted by the

authors. These data support a rapid initial clearance of inhaled vanadium occurring on the

first day of work followed by a slower clearance phase that was not complete 38 h after

the end of exposure (Hauser et al., 1998).

Kucera et al. (1998) analysed vanadium in biological samples from workers engaged in

the production of vanadium pentoxide by a hydrometallurgical process and occupationally

non-exposed controls. Average exposure time was 9.2 years (range, 0.5–33 years). Concen-

trations of vanadium in workplace air samples were high (range, 0.017–4.8 mg/m

3

). Con-

centrations of vanadium in the blood of a subsample of workers was 12.1 

± 3.52 µg/L (geo-

metric mean 

± GSD) compared with 0.055 ± 1.41 µg/L among the non-exposed controls.

Vanadium concentrations in morning urine were 29.2 

± 3.33 µg/L in exposed workers and

0.203 

± 1.61 µg/L for the non-exposed. The finding of high concentrations in morning urine

is compatible with the fact that long-term exposure results in vanadium accumulation in the

bone from which it can be released slowly.

Vanadium pentoxide was found to be rapidly absorbed following inhalation exposure,

but poorly through dermal contact or when ingested as ammonium vanadyl tartrate (Dimond

et al., 1963; Gylseth et al., 1979; Kiviluoto et al., 1981; Ryan et al., 1999). When given

orally, 0.1–1% is absorbed from the gut, although absorption of more soluble vanadium

compounds is greater. About 60% of absorbed vanadium is excreted in the urine within 24 h

(McKee, 1998). Based on samples from autopsies, vanadium was found to be distributed to

VANADIUM PENTOXIDE

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