Indium - Toxicology of Metals - page 560

1933; Yoshikawa and Hasegawa, 1971). Administra-
tion of ionic indium at a concentration of 5 mg/L in
drinking water has also been reported to cause mild
growth-depression in mice (Schroeder and Mitchener,
1971). Other studies (Fowler et al ., 1983; Woods and
Fowler, 1982; Woods et al ., 1979) concerning the intra-
cellular mechanisms of indium-induced cell injury
have demonstrated marked disruption of the endo-
plasmic reticulum associated with marked alteration
of cellular heme metabolism in both hepatocytes and
renal proximal tubule cells.
Studies by Conner et al . (1993) demonstrated both
altered protein expression patterns in kidneys of ham-
sters treated with indium, arsenic, or indium arsenide
particles. These investigators (Conner et al ., 1995) also
demonstrated indium, arsenic, and indium arsenide-
specifi c proteinuria patterns in hamsters treated in vivo
with these agents 10 and 30 days after treatment.
Intratracheal exposure of rats to indium selenide
has been reported to produce acute pulmonary toxicity
in rats characterized by a marked infl ammatory reac-
tion (Morgan et al ., 1995). Similar fi ndings of infl amma-
tion linked to oxidative stress were observed in male
and female rats exposed to an indium phosphide aero-
sol for 6 hours/day, 5 days/week for up to 105 weeks
(Gottschilling et al ., 2001). In vitro studies by Okada
et al . (2002) demonstrated mild toxicity to alveolar
macrophages and no evidence of cell death after in vivo
exposure of hamsters to particles of ferric oxide (60

14 weeks, and alveolar and bronchiolar carcinomas
were noted in both male and female mice.
The developmental toxicity of indium chloride has
been studied by Nakajima and coworkers in rats (1998;
1999) in rats and mice (Nakajima et al ., 2000). These
investigators concluded that both rats and mice were
susceptible to embryo toxicity after parenteral admin-
istration but that mice were less susceptible than rats
to the teratogenic effects of this element. Ungvary
and coworkers (2000; 2001) and Morvai and cowork-
ers (2001) studied the embryotoxic and teratogenic
effects of indium chloride administration in rabbits
and rats (Ungvary et al ., 2000), on the hemodynam-
ics of the placenta in rats (Morvai et al ., 2001a), and on
chondrogenic ossifi cation in rats (Ungvary et al ., 2001).
Overall, the results of these studies show altered pla-
cental hemodynamics and a number of embryo lethal
and teratogenic effects in rats involving normal limb
ossifi cation.
The testicular toxicity of indium arsenide was eval-
uated by Omura et al ., (1996a,b), who found no evi-
dence of testicular toxicity for this compound at doses
of 7.7 mg/kg administered by intratracheal instillation
a total of 14 times.
Implantation of indium-treated silver discs into rabbits
has been found to produce only foreign body reactions
(Harrold et al ., 1943).

µ g)

7.2.2 Humans

and indium arsenide over a dose range of 2-20 g InAs

per animal. In vitro exposure studies of rat thymocytes
to soluble indium chloride were found to induce apop-
tosis (Bustamente et al ., 1997). The pulmonary toxicity
of indium phosphide was studied in rats by Oda (1997)
after intratracheal instillation of at doses of 0, 1.2, 6.0,
and 62

µ

One case of pulmonary fi brosis has been reported in
a person exposed to indium-tin oxide by inhalation for
4 years in a fl at panel plasma manufacturing plant in
Japan (Homma, et al ., 2005).

µ g/kg. Eight days after treatment, only rats at

7.3 Carcinogenicity, Mutagenicity, and
Teratogenicity
There are a number of published studies on the
carcinogenicity or mutagenicity of indium phosphide
(Gottschilling et al . 2001; Gunnels, 2001). The IARC
has determined that indium phosphide is a probable
human carcinogen (2A) on the basis of these data
coupled with the in vitro studies by Bustamente et al .
(1997) that demonstrated the ability of In to induce
apoptosis in rat thymocytes. On the basis of this evalu-
ation and the increasing use of indium compounds
in nanotechnology, it may be prudent to revisit cur-
rent occupational exposure standards such as that of
ACGIH that is currently 0.1 mg In/m 3 . Intravenous
administration of ionic indium to pregnant hamsters
has been reported to produce malformations of the
fetal digits at doses <1 mg/kg and embryo lethality
at higher doses of 2-20 mg/kg after injection on day 8

the 62- g/kg dose level had pulmonary infl ammation.

Tanaka and coworkers (1996; 2000) studied the chronic
comparative pulmonary toxicity of indium phosphide
and indium arsenide particles (Tanaka et al ., 1996) and
indium arsenide, arsenic trioxide, and gallium arse-
nide particles (Tanaka et al ., 2000) in hamsters. They
found pulmonary infl ammation, fi brotic changes, and
evidence of pulmonary squamous cell metaplasia and
bronchial cell hyperplasia after 8 weeks of treatment
(Tanaka et al ., 2000) and that indium arsenide was the
most toxic compound to the lung. The pulmonary tox-
icity of indium arsenide and other III-V semiconduc-
tor compounds has been recently reviewed by Tanaka
(2004) in relation to cancer. The National Toxicology
Program (Gunnels et al . (2001) studied the toxicity of
indium phosphide after inhalation of indium phos-
phide particulates by mice and rats at 14 weeks and
2 years. Pulmonary infl ammation was observed at

µ