Vanadium pentoxide

after treatment with a single intraperitoneal injection of vanadium pentoxide (5 mg/kg bw)

on day 12 of gestation; 1, 4, 24 or 48 h after a single treatment (5 mg/kg bw) on days 16–18

of gestation; or 120 h after the final treatment with 0.33, 1 or 3 mg/kg bw given daily on

days 6–15 of gestation. The concentrations of vanadium in maternal blood, placenta and

fetus were elevated after these different treatments in comparison with those of the respec-

tive untreated groups. The vanadium concentration in fetuses increased with increasing

doses, suggesting that the embryo/fetus accumulated vanadium (Zhang et al., 1991a).

(ii)

Effects on reproductive organs and fertility

Male CD-1 mice were treated intraperitoneally with 8.5 mg/kg bw vanadium pentoxide

once every 3 days for 60 days. Groups of five animals were killed every 10 days after the

beginning of treatment. Twenty-four hours after the last injection, the males were mated

with untreated females. A decrease in fertility rate, implantations, live fetuses and fetal

weight, and an increase in the number of resorptions/dam was observed. In males, sperm

count and motility were impaired as treatment advanced and the presence of abnormal

sperm was observed on days 50 and 60 of treatment (Altamirano-Lozano & Alvarez-

Barrera, 1996; Altamirano-Lozano et al., 1996).

In a National Toxicology Program study (2002), reduced epididymal sperm motility

was observed in B6C3F

1

mice exposed to vanadium pentoxide by inhalation (8- and

16 mg/m

3

dose groups) for 3 months. There were no effects on estrous cycle parameters

in females. No effects were seen on reproductive parameters in male and female F344/N

rats exposed by inhalation to 4, 8 or 16 mg/m

3

vanadium pentoxide (National Toxicology

Program, 2002).

To evaluate the effect of vanadium pentoxide on the newborn rats, Altamirano et al.

(1991) injected 12.5 mg/kg bw vanadium pentoxide intraperitoneally into male and

female prepubertal CII-ZV rats every 2 days (from birth to 21 days), and into female rats

from day 21 to the day of the first vaginal estrus. No changes in vaginal opening nor in

the estrous cycle were observed in either prepubertal or adult female rats; however, the

ovulation rate was reduced in the treated adult females. No differences were observed in

the weights of ovaries, uterus, adrenal gland or pituitary gland, compared to those of

untreated rats; the weights of thymus, liver, kidneys and submandibular glands of new-

born treated females were similar to those of controls. However, when treatment began at

21 days of age, an increase in the weight of thymus, submandibular glands and liver was

observed. In male prepubertal rats, an increase was observed in the weight of seminal

vesicles, thymus and submandibular glands but not of testis and prostate of animals

treated with vanadium from birth to 21 days. The results indicate that, as observed with

other metals, the toxicological effects of vanadium pentoxide differ in males and females,

with toxicity in prepubertal rats being higher in males than in females.

(iii)

Developmental effects

To evaluate the effects of vanadium pentoxide on the embryonic and fetal develop-

ment of mice, Wide (1984) injected pregnant albino NMRI mice via the tail veins with

IARC MONOGRAPHS VOLUME 86

268

pp227-292.qxp  31/05/2006  09:49  Page 268

---

1.5 mM/animal [273 

µg/animal ∼ 10 mg/kg bw] vanadium pentoxide on day 3 or day 8

of gestation. All animals were killed 2 days before parturition (17th day of pregnancy) and

fetuses were dissected and examined. Treatment with vanadium pentoxide on day 8 of

gestation did not induce teratogenic effects but reduced fetal skeletal ossification.

In a study of the developmental toxicity of vanadium pentoxide, Zhang et al. (1991b)

injected pregnant female NIH mice intraperitoneally with 5 mg/kg bw vanadium pentoxide

per day on different days of gestation (days 1–5, 6–15, 7, 8, 9, 10, 11 or 14–17 of

pregnancy). No effects on pre-implantation were found, nor malformations nor premature

birth. However, an increased frequency of resorptions or fetal death was observed in ani-

mals treated on days 7, 6–15, and 14–17 of gestation. Delayed skeletal ossification was

noted in mice treated on days 6–15, 8, 10 and 14–17 of gestation. The authors suggested

that vanadium pentoxide acted as a weak developmental toxicant but not a teratogen. 

To evaluate the teratogenic effects of vanadium pentoxide, female CD-1 mice were

injected intraperitoneally once daily on days 6–15 of gestation with 8.5 mg/kg bw. Vana-

dium did not cause significant adverse effects on the number of live and dead fetuses

(including resorptions) nor on fetal implants; however, a decrease in fetal weight and a

delay in skeletal ossification were observed. Limb shortening was the most frequent alte-

ration. No maternal toxicity was detected (Altamirano-Lozano et al., 1993). 

In female Wistar rats exposed to 0.33, 1 or 3 mg/kg bw vanadium pentoxide from days

6–15 of gestation, the highest dose was toxic. Increased fetal mortality and external or

skeletal malformations with delay in ossification were also observed (Zhang et al., 1993a).

Similar results were found in one further study in Wistar rats (Zhang et al., 1993b).

(b)

In-vitro studies

Li et al. (1995) investigated the toxicological effects of vanadium pentoxide (0.125,

0.25, 0.5, 2 or 3 mM) in rat Leydig cells in vitro and found no obvious relationship between

testosterone secretion and the concentration of vanadium. The authors concluded that

Leydig cells are not a target for vanadium pentoxide. This is in agreement with results of

in-vivo studies previously reported by Altamirano et al. (1991) who had shown that the

weight of the testis and prostate were not increased after vanadium treatment of rats (see

Section 4.3.2(ii)).

Altamirano-Lozano et al. (1997, 1998a) tested the reprotoxic effects of various metal

compounds on boar spermatozoa in vitro. Sperm were exposed to vanadium pentoxide

(5.5, 16.5, 27.5, 55, 110 or 220 

µM) and motility was analysed 0, 1, 2, 3, 4, 5 and 6 h after

treatment. A dose- and time-dependent reduction in sperm motility was observed, in

accordance with results obtained in vivo in mice by the same group (Altamirano-Lozano

et al., 1996).

VANADIUM PENTOXIDE

269

pp227-292.qxp  31/05/2006  09:49  Page 269

---