Developmental toxicity of indium chloride by intravenous or oral administration in rats

Usami

Nakazawa

et al. 2008

Congenital Anomalies

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Indium, a precious metal classified in group 13 (IIIB) in the periodic table, has been used increasingly in the semiconductor industry. Because indium is a rare metal, technology for indium recycling from transparent conducting films for liquid crystal displays is desired, and its safety evaluation is becoming increasingly necessary. The developmental toxicity of indium in experimental animals was summarized. The intravenous or oral administration of indium to pregnant animals causes growth inhibition and the death of embryos in hamsters, rats, and mice. The intravenous administration of indium to pregnant animals causes embryonic or fetal malformation, mainly involving digit and tail deformities, in hamsters and rats. The oral administration of indium also induces fetal malformation in rats and rabbits, but requires higher doses. No teratogenicity has been observed in mice. Caudal hypoplasia, probably due to excessive cell loss by increased apoptosis in the tailbud, in the early postimplantation stage was considered to account for indium-induced tail malformation as a possible pathogenetic mechanism. Findings from in vitro experiments indicated that the embryotoxicity of indium could have direct effects on the conceptuses. Toxicokinetic studies showed that the embryonic exposure concentration was more critical than the exposure time regarding the embryotoxicity of indium. It is considered from these findings that the risk of the developmental toxicity of indium in humans is low, unless an accidentally high level of exposure or unknown toxic interaction occurs because of possible human exposure routes and levels (i.e. oral, very low-level exposure).

“…2006). Our previous study (Nakajima et al. 1998) clearly showed the teratogenicity of indium by a single intravenous administration to pregnant Wistar rats on GD 9.…”

Section: Pathogeneses and Mechanismsmentioning

confidence: 90%

“…By the single intravenous administration of indium chloride to pregnant Wistar rats on GD 9, fetal malformations of the tail and digits (e.g. kinked tail, brachyury, and oligodactyly) were observed at high incidences at 0.4 mg/kg (Nakajima et al. 1998).…”

Section: Species Differencesmentioning

confidence: 99%

Developmental toxicity of indium: Embryotoxicity and teratogenicity in experimental animals

Usami

Nakazawa

et al. 2008

Congenital Anomalies

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“…administration, which was not covered in the preliminary toxicokinetic experiments in the previous studies [2,3], is required. This is partly supported by the fact that the embryotoxic dose of indium by i.v.…”

Section: Discussionmentioning

confidence: 99%

“…Repeated oral administration of indium trichloride (InCl 3 ) to pregnant mice from days 6 through 15 of pregnancy at 250 mg/kg/day caused fetal weight decrease and fetal death, but no increase in fetal malformations [3]. A disposition study in male mice showed that the peak plasma indium concentration by oral administration of 250 mg/ kg was only 1.6 µg/ml [3], which is comparable to the serum concentration in the pregnant rat by single oral administration [2]. A disposition study in male mice showed that the peak plasma indium concentration by oral administration of 250 mg/ kg was only 1.6 µg/ml [3], which is comparable to the serum concentration in the pregnant rat by single oral administration [2].…”

Section: Introductionmentioning

confidence: 97%

See 1 more Smart Citation

Comparative developmental toxicity study of indium in rats and mice

Teratog. Carcinog. Mutagen.

Takahashi

Sasaki

et al. 2000

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The developmental toxicity of indium was examined in both rats and mice using comparable experimental protocols. Pregnant rats received a single intravenous administration of indium trichloride (InCl(3)) at 0.4 mg In/kg, on day 9, 10, or 11 of pregnancy and their fetuses were examined on day 20. Pregnant mice were treated in the same manner at 0.8 or 1.6 mg In/kg on day 7, 8, or 9 of pregnancy and their fetuses were examined on day 18. In rats, indium caused fetal weight decrease and fetal gross malformations, such as brachyury, kinked tail, cleft palate, and oligodactyly, most severely by the administration on day 10. In mice, however, indium did not cause fetal gross malformations, although it caused fetal weight decrease at 0.8 mg In/kg or more and fetal death at 1.6 mg In/kg, most severely by the administration on day 8. It was concluded from these results that rats and mice were susceptible to the embryotoxicity of indium at similar developmental stages in the early organogenetic period, but mice were less susceptible to the teratogenicity of indium than rats in terms of gross malformation. Toxicokinetic factors may be involved in this different susceptibility. Teratogenesis Carcinog. Mutagen. 20:219-227, 2000.

Developmental toxicity of indium in cultured rat embryos

Teratog. Carcinog. Mutagen.

Sasaki

Kobayashi

et al. 1999

Self Cite

Developmental toxicity of indium was examined using rat embryo culture with reference to toxicokinetics. Rat embryos at day 9.5 of pregnancy were cultured for 48 h under various exposure conditions to indium trichloride. Indium was embryotoxic to cultured rat embryos at concentrations ranging from 25 to 50 μM for 24 h exposure according to the embryonic age, and the exposure concentration was more critical than the exposure time. The embryotoxic concentrations were comparable to the serum concentration at a developmentally toxic dose by intravenous administration in an in vivo experiment. It was considered from these results that the developmental toxicity of indium is a direct effect on the embryo or yolk sac and that weak developmental toxicity of indium by oral administration was due to low exposure concentrations in the embryo. Teratogenesis Carcinog. Mutagen. 19:205–209, 1999. © 1999 Wiley‐Liss, Inc.