Posted 02 September 2007 - 06:17 PM
Fundam Appl Toxicol. 1995 Aug;27(1):140-8. Links
The reproductive and developmental toxicity of indium in the Swiss mouse.Chapin RE, Harris MW, Hunter ES 3rd, Davis BJ, Collins BJ, Lockhart AC.
Reproductive Toxicology Group, National Toxicology Program/NIEHS, Research Triangle Park, North Carolina 27709, USA.
Indium is increasingly used in a variety of industries, and while there are few studies of its developmental toxicity, ther are no reports of its potential reproductive toxicity. These studies were undertaken to investigate the possible reproductive toxicity of indium and to determine the relative vulnerability of males and females. We used, initially, a 21-day combined developmental/reproductive toxicity protocol. Oral exposures to InCl3 ( < or = 250 mg/kg) were without effect on the male reproductive system or liver. A kidney effect was demonstrated in males by a decrease in urinary N-acetyl glucosaminidase. The ability of females to become pregnant was unaffected. However, fetal development was adversely affected, manifested as increased intrauterine deaths in the presence of reduced maternal weight gain. A developmental toxicity study identified no increase in fetal malformations, but verified the increased fetal deaths, in the absence of effects on adjusted maternal body weight. In vitro toxicity studies showed that the embryolethality was at least in part a result of direct toxicity to the conceptus, with effective doses in the low micromolar range. A limited disposition study showed that fetuses contained low micromolar concentrations of indium, more indium than maternal liver, and comparable to levels that were toxic in vitro. Although studies of greater exposure duration are required for risk assessment, these data indicate that fetal development is likely to be more affected by indium than female or male reproduction, with adverse effects occurring at low micromolar levels in vivo and at exposures that may or may not affect body weight.
Developmental toxicity of indium in cultured rat embryos
Mikio Nakajima 1 *, Masanori Sasaki 1, Youshiro Kobayashi 1, Yasuo Ohno 2, Makoto Usami 2
1Laboratory for Toxicological Research, Institute for Life Science Research, Asahi Chemical Industry Co., Ltd., Shizuoka, Japan
2Division of Pharmacology, National Institute of Health Sciences, Tokyo, Japan
email: Mikio Nakajima (a8586381@ut.asahi-kasei.co.jp)
*Correspondence to Mikio Nakajima, Laboratory for Toxicological Research, Institute for Life Science Research, Asahi Chemical Industry Co., Ltd., 632-1, Mifuku, Ohito-cho, Tagata-gun, Shizuoka 410-2321, Japan
Keywords
rat; indium trichloride; developmental toxicity; embryo culture; toxicokinetics
Abstract
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 M 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.
Title: Comparative pulmonary absorption, distribution, and toxicity of copper gallium diselenide, copper indium diselenide, and cadmium telluride in Sprague-Dawley rats.
Author: Morgan, D L : Shines, C J : Jeter, S P : Blazka, M E : Elwell, M R : Wilson, R E : Ward, S M : Price, H C : Moskowitz, P D
Citation: Toxicol-Appl-Pharmacol. 1997 Dec; 147(2): 399-410
Abstract: Copper gallium diselenide (CGS), copper indium diselenide (CIS), and cadmium telluride (CdTe) are novel compounds used in the photovoltaic and semiconductor industries. This study was conducted to characterize the relative toxicities of these compounds and to evaluate the pulmonary absorption and distribution after intratracheal instillation. Female Sprague-Dawley rats were administered a single equimolar dose (70 mM) of CGS (21 mg/kg), CIS (24 mg/kg), CdTe (17 mg/kg), or saline by intratracheal instillation. Bronchoalveolar lavage fluid (BALF) protein, fibronectin, inflammatory cells, lung hydroxyproline, and tissue distribution were measured 1, 3, 7, 14, and 28 days after instillation. Relative lung weights were significantly increased in CIS- and CdTe-treated rats at most time points. Inflammatory lesions in the lungs consisting of an influx of macrophages, lymphocytes, and PMNs were most severe in CdTe-treated rats, intermediate in CIS-treated rats, and minimal in rats receiving CGS. Hyperplasia of alveolar type 2 cells was present in CIS- and CdTe-treated rats and was greatest in CdTe-treated rats. Pulmonary interstitial fibrosis was observed in CdTe-treated rats at all time points. All three compounds caused marked increases in total BALF cell numbers, with the greatest increase observed in CIS-treated rats. BALF protein, fibronectin, and lung hydroxyproline were significantly increased in all treated animals and were highest in CdTe-treated animals. There was no apparent pulmonary absorption or tissue distribution of CGS. Indium levels increased in extrapulmonary tissues of CIS-treated rats, although Cu and Se levels remained unchanged. CdTe was absorbed from the lung to a greater extent than CGS and CIS. Cd and Te levels decreased in the lung and increased in extrapulmonary tissues. Of these compounds CdTe presents the greatest potential health risk because it causes severe pulmonary inflammation and fibrosis and because it is readily absorbed from the lung may potentially cause extrapulmonary toxicity.
S. A. Mangoura1, A. Strack1, W. Legrum1 and K. J. Netter1
(1) Institut für Pharmakologie und Toxikologie der Philipps-Universität, Lahnberge, D-3550 Marburg, Federal Republic of Germany
Received: 30 September 1988 Accepted: 15 February 1989
Summary Indium pretreatment of rats and mice has been reported to decrease the concentration of cytochrome P-450, thereby reducing the activity of some cytochrome P-450 dependent enzymatic reactions. The present study reveals that pretreatment of C57B1/6JHan mice of both sexes with one s. c. dose of 120 mg of In2(SO4)3 · 5 H2O per kg of body weight decreases the concentration of cytochrome P-450 to about 65% of control levels.
Neither cytochrome b5 nor NADPH-cytochrome P-450 reductase is affected. Hepatic microsomal ethoxyresorufin O-deethylase activity declines to about 75% of control values. In contrast, with coumarin substrates, a sex dependence in the direction of change is observed: in female mice indium decreases the activity to about 75%, whereas in males it enhances the activity to 140%. Moreover, with 7-(methoxy-14C)coumarin as substrate, indium-pretreated male mice exhale about 180% and females about 65% of 14C02 compared to the corresponding controls. A close correlation between the in vivo and in vitro effects of indium on the metabolism of the coumarin derivatives is suggested. After isolation and purification of cytochrome P-450, SDS-PAGE indicates in indium-pretreated male mice an intensification of a 48.5 kDa protein band which is decreased in females. Immunological studies using antibodies raised against control female cytochrome P-450 show cross reactivity among all microsomes used in these experiments. High percentages of inhibition occur in microsomes with high molecular activity towards coumarin derivatives. The in vitro kinetics of antibody-inhibited O-deethylation of 7-ethoxycoumarin seems to obey a non- or partial-competitive type of inhibition. Indium pretreatment of mice produces sex-dependent effects on the metabolism of coumarin derivatives.
Toxicity of indium arsenide, gallium arsenide, and aluminium gallium arsenide
Akiyo Tanaka,
Department of Hygiene, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan
Received 1 July 2003; accepted 8 October 2003. Available online 18 March 2004.
Abstract
Gallium arsenide (GaAs), indium arsenide (InAs), and aluminium gallium arsenide (AlGaAs) are semiconductor applications. Although the increased use of these materials has raised concerns about occupational exposure to them, there is little information regarding the adverse health effects to workers arising from exposure to these particles. However, available data indicate these semiconductor materials can be toxic in animals. Although acute and chronic toxicity of the lung, reproductive organs, and kidney are associated with exposure to these semiconductor materials, in particular, chronic toxicity should pay much attention owing to low solubility of these materials. Between InAs, GaAs, and AlGaAs, InAs was the most toxic material to the lung followed by GaAs and AlGaAs when given intratracheally. This was probably due to difference in the toxicity of the counter-element of arsenic in semiconductor materials, such as indium, gallium, or aluminium, and not arsenic itself. It appeared that indium, gallium, or aluminium was toxic when released from the particles, though the physical character of the particles also contributes to toxic effect. Although there is no evidence of the carcinogenicity of InAs or AlGaAs, GaAs and InP, which are semiconductor materials, showed the clear evidence of carcinogenic potential. It is necessary to pay much greater attention to the human exposure of semiconductor materials.
Author Keywords: Semiconductor materials; Indium arsenide; Gallium arsenide; Aluminium gallium arsenide; Pulmonary toxicity; Hamster; Intratracheal instillations
Other keywords: MOST TOXIC!
Comparative Toxicity and Pharmacodynamics of Ionic Indium Chloride and Hydrated Indium Oxide
Frank P. Castronovo, Jr. and Henry N. Wagner, Jr.
The Johns Hopkins Medical Institutions, Baltimore, Maryland
Correspondence: For reprints contact: F. P. Castronovo, Dept. of Radiology, Massachusetts General Hospital, Boston, Mass. 02114.
ABSTRACT
Interest in the toxicity and pharmacodynamics of indium compounds resulted from their use as diagnostic radiopharmaceuticals. Indium-113 (T1/2 1.7hr) is administered intravenously as ionic indium chloride, colloidal hydrated indium oxide, and macroaggregated 113In-iron hydroxide. Indium-111 (T1/2 2.8 days) is also used in clinical nuclear medicine. Studies included determination of the (LD50/4 days) of ionic and colloidal indium and a pharmacodynamic evaluation of tracer dose levels of these compounds using 114mIn (T1/2 50 days). Initial biological distribution, subsequent translocation, whole-body retention, and excretion were investigated. Colloidal hydrated indium oxide was found to be 40 times more toxic than ionic indium chloride, the principal damage being to the organs of the reticuloendothelial system. Ionic indium chloride caused acute tubular necrosis of the kidneys. Hydrated indium oxide accumulated primarily in the liver, spleen, and bone marrow and was mainly excreted in the feces. Ionic indium became protein bound after administration with subsequent translocation to the kidney and liver and was excreted mainly in the urine.
Most urine and feces...there goes the cost, but finding a home in the liver, spleen, kidneys and bone marrow. Awesome.
Title Long Term Pulmonary Toxicity of Indium Arsenide and Indium Phosphide Instilled Intratracheally in Hamsters
Author Koji YAMAZAKI1, 2, Akiyo TANAKA1, Miyuki HIRATA1, Minoru OMURA1, Yuji MAKITA1, Naohide INOUE1, Kenji SUGIO2, Keizo SUGIMACHI2
Organization 1Department of Hygiene and
2Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University
Keywords semiconductor materials, indium arsenide, indium phosphide, intratracheal instillation, pulmonary toxicity, proliferative activity
Correspondence K. Yamazaki, Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
Abstract Long Term Pulmonary Toxicity of Indium Arsenide and Indium Phosphide Instilled Intratracheally in Hamsters: Koji YAMAZAKI, et al. Department of Hygiene, Graduate School of Medical Sciences, Kyushu University-We examined the long-term toxicological effects of III-V semiconductor particles on laboratory animals. Eight-week-old male Syrian golden hamsters were given 4 mg/kg indium arsenide (InAs) or 3 mg/kg indium phosphide (InP) particles, both containing 2.4 mg/kg as indium, intratracheally twice a week for 8 weeks. Control hamsters were given only a vehicle, phosphate buffer solution. Over a 2-yr period, these animals were euthanized serially and the biological effects were determined. Weight gain was significantly suppressed in both InAs and InP groups, compared to the control group, with greater suppression in the InAs group. The serum indium concentration in the InAs group was about twice as high as that in the InP group, in each period. Histopathologically, severe pulmonary inflammation and localized lesions with bronchiolo-alveolar cell hyperplasia were present in both InAs and InP groups from just after the last administration. The localized lesions gradually transformed to proteinosis-like lesions with periodic acid Schiff reagent positive exudation after 16 wk. By means of immunostaining of proliferating cell nuclear antigen and argyrophilic proteins associated with nucleolar organizer regions staining, proliferative activities were evidenced in the localized lesions at each time and were noticeable in their early stage. K-ras, a known oncogene, was not mutated in association with these lesions. In conclusion, InAs and InP particles caused severe systemic toxicity and pulmonary localized hyperplastic lesions with proliferative activity were derived via the respiratory route. Neoplastic change was nil even in a 2-yr observation period.
One PDF showed testicular damage to hampster exposed to Indium Tin Oxide.
Acute Oral Toxicity and Dermal Irritation Test of Indium Chloride
Éva Szakmáry1, Mária Mándy1, Márta Kovács2, Erzsébet Tátrai1, and György Ungváry2
1 National Institute of Occupational Health, József Fodor National Center for Public Health, Budapest, Hungary
2 József Fodor National Center for Public Health, Budapest, Hungary
Corresponding author: Prof. György Ungváry MD., PhD., DSc.
Fodor József National Center for Public Health
P.O. Box 22.
H-1450, Budapest, Hungary
Telephone: (+36) 1-215-5491
Fax number: (+36)1-215-6891
E-mail: ungvary@fjokk.hu
CEJOEM 2001, Vol.7. No.1.:60-65
--------------------------------------------------------------------------------
Key words:
Indium chloride, acute oral toxicity, acute dermal irritation
--------------------------------------------------------------------------------
Abstract:
Acute oral and dermal toxicity effects of indium chloride were studied on SPRD rats and New Zealand rabbits. The tests were performed according to OECD Guidelines for Test8ing of Chemicals. In acute oral toxicity study of indium chloride, the LD50 values amounted to 1983 mg/kg both in male and female rats. The confidence interval values were LD84–2283 mg/kg and LD16–1741 mg/kg, respectively. The dose level of 500 mg of indium chloride caused severe irreversible dermal damages, i.e., it proved to be irritative and corrosive. On the basis of our earlier and present studies, the toxicity and hazardousness of indium chloride can be classified as follows: Harmful. Danger symbol: Xn harmful, C corrosive. R numbers/phrases: 22-34-61, S numbers/phrases: 24/25-26-27/28-46.
Toxicity of a Low Level of Indium Phosphide (InP) in Rats after Intratracheal Instillation
Kenichi ODA1)
1) Department of Preventive Medicine and Public Health, School of Medicine, Keio University
[Received: 1996/09/30]
[Released: 2007/03/29]
Abstract:
To clarify the instillation toxicity of low level of indium phosphide (InP), 0, 1.2, 6.0 and 62.0μg/kg body weight of InP particles were instilled intratracheally in male Fischer 344 rats, and the effects of InP were examined on the following day (day 1) and on the 8th day (day 8) after instillation. Indium was measured but not detected in the serum, liver, kidney, spleen, thymus and brain. Dose-related mild elevation of superoxide dismutase (SOD) activity and lactate dehydrogenase (LDH) activity in bronchoalveolar lavage fluid (BALF) were found on day 1 without increases of inflammatory cells and total protein (TP) in BALF, which suggested the response of neutrophils and alveolar macrophages to instilled InP, and/or the manifestation of a very early stage of inflammation. Only in the 62.0μg/kg-instilled group on day 8, were neutrophils, lymphocytes, TP, LDH, total phospholipid and total cholesterol in BALF increased, and desquamation of alveolar epithelial cells and amorphous exudate in alveolar lumen observed by histopathological examination. These results suggested that InP caused pulmonary inflammation and epithelial cell damage up to 8 days following instillation dose of 62.0μg/kg, but that its effect was considered irrelevant at instillation doses of 6.0 μg/kg or below in rat.
Keywords: