exposed to the lowest dose (approximately 0.22
µg/day). These results are likely to be
explained by altered pulmonary function in the higher-dose groups, resulting in lung
clearance rates that were lower than in the low-dose group. Lung clearance half-lives were
37, 59 and 61 days for the high, medium and low exposure groups, respectively, i.e. much
longer than in the 16-day study (see above). Apparently, vanadium is cleared more rapidly
from the lungs of rats exposed to vanadium pentoxide for short periods of time or at low
concentrations repeatedly for longer periods. From the deposition curves over the 542
days of the study, the estimated total vanadium lung doses were 130, 175 and 308
µg for
the 0.5-, 1- and 2-mg/m
3
exposure groups, respectively. Normalized lung doses (
µg vana-
dium/mg vanadium pentoxide per m
3
) were not constant but decreased with increasing
exposure, i.e., 260, 175 and 154
µg per mg/m
3
for low, medium and high dose groups,
respectively. This decrease was due to the reduced deposition of vanadium with increasing
exposure concentration. Rats retained approximately 10–15% of the estimated lung dose
on day 542. Concentrations of vanadium in blood were much lower than in lung and were
only marginally higher in exposed rats than in controls. Vanadium concentrations in blood
of exposed animals peaked on days 26 or 54, then declined throughout the rest of the
study. Because the changes were small, it was difficult to distinguish between decreased
absorption from the lung, resulting from reduced deposition, and increased elimination
from the blood (National Toxicology Program, 2002).
Kyono et al. (1999) showed that the health status of the lung influences the deposition
and retention of vanadium. In an experimental model for nickel-induced bronchiolitis in
rats, bronchiolitic rats and control animals were exposed to vanadium pentoxide
(2.2 mg/m
3
; MMAD, 1.1
µm) for 5 h. The vanadium content in the lungs of controls was
higher (about 100%) than in bronchiolitic rats after 1 day of exposure, but 2 days later the
retention was 20% in controls and 80% in bronchiolitic rats. Elimination of vanadium was
found to be much slower in bronchiolitic rats.
(ii)
Intratracheal instillation
Several studies have shown that after intratracheal instillation of vanadium pentoxide
in rats there was generally a rapid initial clearance of up to 50% during the first hour, a
second phase with a half-life of about 2 days and a third phase during which vanadium
remained in the lung for up to 63 days (Oberg et al., 1978; Conklin et al., 1982; Rhoads
& Sanders, 1985).
(iii)
Oral administration
Administration of vanadium pentoxide by gavage resulted in absorption of 2.6% of
the dose through the gastrointestinal tract 3 days after the treatment (Conklin et al., 1982).
Distribution was mainly to bone, liver, muscle, kidney, spleen and blood. Chronic
treatment with inorganic vanadium salts or organic vanadium has been shown to result in
significant accumulation in the bone, spleen and kidney (Mongold et al., 1990; Thompson
& McNeil, 1993; Yuen et al., 1993).
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Studies with non-diabetic and streptozotocin-diabetic rats given vanadyl sulfate in
their drinking-water (0.5–1.5 mg/mL) for 1 year showed concentrations of vanadium to
be in the following order [of distribution]: bone > kidney > testis > liver > pancreas >
plasma > brain. Vanadium was found to be retained in these organs 16 weeks after cessa-
tion of treatment while the concentrations in plasma were below the limits of detection at
this time (Dai et al., 1994).
(b)
Cellular studies
Edel and Sabbioni (1988, 1989) showed accumulation of vanadium in hepatocytes
and kidney cells (in the nucleus, cytosol and mitochondria) in rats exposed to vanadium
as radioactive
48
V (V) pentavanadate ions and
48
V (IV) tetravalent ions by intratracheal
instillation, oral administration or intravenous injection.
Cell cultures (human Chang liver cells, bovine kidney cells), incubated in medium
supplemented with vanadium in the form of vanadate, have been shown to accumulate
this element in the nucleus and mitochondria (Bracken et al., 1985; Stern et al., 1993; Sit
et al., 1996). In BALB/3T3 C1A31-1-1 cells incubated in the presence of sodium vana-
date and vanadyl sulfate, the cellular retention of both compounds was similar. After
exposure to a non-toxic dose (1
µM for 48 and 72 h), nearly all vanadium was present in
the cytosol, but at a toxic dose (10
µM for 48 and 72 h), 20% of the vanadium was found
in cellular organelles (Sabbioni et al., 1991).
4.2
Toxic effects
4.2.1
Humans
In humans, acute vanadium poisoning can manifest itself in a number of symptoms
including eye irritation and tremors of the hands (Lewis, 1959). In addition, a greenish
colouration of the tongue has been observed in humans exposed to high concentrations of
vanadium pentoxide and is probably due to the formation of trivalent and tetravalent
vanadium complexes (Wyers, 1946). The green colour disappears within 2–3 days of
cessation of exposure (Lewis, 1959).
(a)
Studies with volunteers
Zenz and Berg (1967) studied the effects of vanadium pentoxide in nine male volun-
teers exposed in an inhalation chamber to concentrations of vanadium pentoxide of 0.1,
0.25, 0.5 or 1.0 mg/m
3
(particle size, 98% < 5
µm) for 8 h, with follow-up periods of 11–19
months. Acute respiratory irritation was reported, which subsided within 4 days after
exposure (see also Section 4.1.1).
No skin irritation was reported in 100 human volunteers after skin patch testing with
1, 2 and 10% vanadium pentoxide in petrolatum (Motolese et al., 1993).
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