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      Studies on the Toxicity and Distribution of Indium Compounds According to Particle Size in Sprague-Dawley Rats

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          Abstract

          Objectives: The use of indium compounds, especially those of small size, for the production of semiconductors, liquid-crystal panels, etc., has increased recently. However, the role of particle size or the chemical composition of indium compounds in their toxicity and distribution in the body has not been sufficiently investigated. Therefore, the aim of this study was to examine the effects of particle size and the chemical composition of indium compounds on their toxicity and distribution. Methods: Male Sprague-Dawley rats were exposed to two different-sized indium oxides (average particle sizes under 4,000 nm [IO_4000] and 100 nm [IO_100]) and one nano-sized indium-tin oxide (ITO; average particle size less than 50 nm) by inhalation for 6 hr daily, 5 days per week, for 4 weeks at approximately 1 mg/m 3 of indium by mass concentration. Results: We observed differences in lung weights and histopathological findings, differential cell counts, and cell damage indicators in the bronchoalveolar lavage fluid between the normal control group and IO- or ITO-exposed groups. However, only ITO affected respiratory functions in exposed rats. Overall, the toxicity of ITO was much higher than that of IOs; the toxicity of IO_4000 was higher than that of IO_100. A 4-week recovery period was not sufficient to alleviate the toxic effects of IO and ITO exposure. Inhaled indium was mainly deposited in the lungs. ITO in the lungs was removed more slowly than IOs; IO_4000 was removed faster than IO_100. IOs were not distributed to other organs (i.e., the brain, liver, and spleen), whereas ITO was. Concentrations of indium in the blood and organ tissues were higher at 4 weeks after exposure. Conclusions: The effect of particle size on the toxicity of indium compounds was not clear, whereas chemical composition clearly affected toxicity; ITO showed much higher toxicity than that of IO.

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          The new toxicology of sophisticated materials: nanotoxicology and beyond.

          It has long been recognized that the physical form of materials can mediate their toxicity--the health impacts of asbestiform materials, industrial aerosols, and ambient particulate matter are prime examples. Yet over the past 20 years, toxicology research has suggested complex and previously unrecognized associations between material physicochemistry at the nanoscale and biological interactions. With the rapid rise of the field of nanotechnology and the design and production of increasingly complex nanoscale materials, it has become ever more important to understand how the physical form and chemical composition of these materials interact synergistically to determine toxicity. As a result, a new field of research has emerged--nanotoxicology. Research within this field is highlighting the importance of material physicochemical properties in how dose is understood, how materials are characterized in a manner that enables quantitative data interpretation and comparison, and how materials move within, interact with, and are transformed by biological systems. Yet many of the substances that are the focus of current nanotoxicology studies are relatively simple materials that are at the vanguard of a new era of complex materials. Over the next 50 years, there will be a need to understand the toxicology of increasingly sophisticated materials that exhibit novel, dynamic and multifaceted functionality. If the toxicology community is to meet the challenge of ensuring the safe use of this new generation of substances, it will need to move beyond "nano" toxicology and toward a new toxicology of sophisticated materials. Here, we present a brief overview of the current state of the science on the toxicology of nanoscale materials and focus on three emerging toxicology-based challenges presented by sophisticated materials that will become increasingly important over the next 50 years: identifying relevant materials for study, physicochemical characterization, and biointeractions.
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            In Search of the Most Relevant Parameter for Quantifying Lung Inflammatory Response to Nanoparticle Exposure: Particle Number, Surface Area, or What?

            Background Little is known about the mechanisms involved in lung inflammation caused by the inhalation or instillation of nanoparticles. Current research focuses on identifying the particle parameter that can serve as a proper dose metric. Objectives The purpose of this study was to review published dose–response data on acute lung inflammation in rats and mice after instillation of titanium dioxide particles or six types of carbon nanoparticles. I explored four types of dose metrics: the number of particles, the joint length—that is, the product of particle number and mean size—and the surface area defined in two different ways. Findings With the exception of the particle size–based surface area, all other parameters worked quite well as dose metrics, with the particle number tending to work best. The apparent mystery of three equally useful dose metrics could be explained. Linear dose–response relationships were identified at sufficiently low doses, with no evidence of a dose threshold below which nanoparticle instillation ceased to cause inflammation. In appropriately reduced form, the results for three different sets of response parameters agreed quite well, indicating internal consistency of the data. The reduced data revealed particle-specific differences in surface toxicity of the carbon nanoparticles, by up to a factor of four, with diesel soot being at the low end. Conclusions The analysis suggests that the physical characterization of nanoparticles and the methods to determine surface toxicity have to be improved significantly before the appropriate dose metric for lung inflammation can be identified safely. There is also a need for refinements in quantifying response to exposure.
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              Pulmonary alveolar proteinosis in workers at an indium processing facility.

              Two cases of pulmonary alveolar proteinosis, including one death, occurred in workers at a facility producing indium-tin oxide (ITO), a compound used in recent years to make flat panel displays. Both workers were exposed to airborne ITO dust and had indium in lung tissue specimens. One worker was tested for autoantibodies to granulocytemacrophage-colonystimulating factor (GM-CSF) and found to have an elevated level. These cases suggest that inhalational exposure to ITO causes pulmonary alveolar proteinosis, which may occur via an autoimmune mechanism.
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                Author and article information

                Journal
                Toxicol Res
                Toxicol Res
                ksot
                Toxicological Research
                The Korean Society Of Toxicology
                1976-8257
                2234-2753
                March 2014
                : 30
                : 1
                : 55-63
                Affiliations
                Toxicity Research Team, Occupational Safety and Health Research Institute, KOSHA, Exporo, Yuseong-Gu, Daejeon, Korea
                Author notes
                Correspondence to: Cheol-Hong Lim, Toxicity Research Team, Occupational Safety and Health Research Institute, KOSHA, 339-30, Exporo, Yuseong-Gu, Daejeon 305-380, Korea E-mail: limch@ 123456kosha.net
                Article
                toxicr-30-55
                10.5487/TR.2014.30.1.055
                4007045
                24795801
                7a4e9855-e448-416e-a8d0-bddaa1f31fcd
                Copyright © 2014, The Korean Society Of Toxicology

                This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 March 2014
                : 30 March 2014
                : 30 March 2014
                Categories
                Articles

                indium,inhalation,nano
                indium, inhalation, nano

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