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The Tohoku Journal of Experimental... Jul 2019Indium is mainly used as indium-tin oxide (ITO), which has a unique character of transparency, and is a requisite in making liquid crystal displays. Pulmonary toxicity... (Review)
Review
Indium is mainly used as indium-tin oxide (ITO), which has a unique character of transparency, and is a requisite in making liquid crystal displays. Pulmonary toxicity of indium compounds in humans were not recognized until the last 2 decades. Several initial human cases of indium-related lung disease, named indium lung, were reported in Japan, with their main pathologic findings being interstitial pneumonia, emphysema and cholesterol crystals-containing granulomas. In 2010, three cases with alveolar proteinosis were reported from the United States and China. As of March 2019, more than 10 cases of interstitial pneumonia-dominant indium lung have been reported. Cross-sectional studies in indium workers indicate that the serum indium concentration (sIn) is closely related to the exposure period, the extent of interstitial as well as emphysematous changes of the lung on high-resolution computed tomography (HRCT) and serum biomarkers of interstitial pneumonia, including KL-6 and surfactant protein-D (SP-D). Longitudinal studies have shown it is possible to reduce the sIn as well as the interstitial shadows on HRCT; however, emphysematous lesions increased progressively in heavily exposed workers, even after cessation of exposure. Early detection is required to prevent irreversible changes. The first case of lung cancer associated with indium lung developed in a nonsmoking ex-worker. He had been diagnosed with indium lung and stopped working in indium processing 17 years before. This suggested there is a need for appropriate screening to detect for complications of lung cancer at early stages for those with indium lung.
Topics: Humans; Indium; Lung; Lung Diseases; Lung Neoplasms; Social Control, Formal; Workplace
PubMed: 31257311
DOI: 10.1620/tjem.248.143 -
Chest Jun 2012Reports of pulmonary fibrosis, emphysema, and, more recently, pulmonary alveolar proteinosis (PAP) in indium workers suggested that workplace exposure to indium...
BACKGROUND
Reports of pulmonary fibrosis, emphysema, and, more recently, pulmonary alveolar proteinosis (PAP) in indium workers suggested that workplace exposure to indium compounds caused several different lung diseases.
METHODS
To better understand the pathogenesis and natural history of indium lung disease, a detailed, systematic, multidisciplinary analysis of clinical, histopathologic, radiologic, and epidemiologic data for all reported cases and workplaces was undertaken.
RESULTS
Ten men (median age, 35 years) who produced, used, or reclaimed indium compounds were diagnosed with interstitial lung disease 4-13 years after first exposure (n = 7) or PAP 1-2 years after first exposure (n = 3). Common pulmonary histopathologic features in these patients included intraalveolar exudate typical of alveolar proteinosis (n = 9), cholesterol clefts and granulomas (n = 10), and fibrosis (n = 9). Two patients with interstitial lung disease had pneumothoraces. Lung disease progressed following cessation of exposure in most patients and was fatal in two. Radiographic data revealed that two patients with PAP subsequently developed fibrosis and one also developed emphysematous changes. Epidemiologic investigations demonstrated the potential for exposure to respirable particles and an excess of lung abnormalities among coworkers.
CONCLUSIONS
Occupational exposure to indium compounds was associated with PAP, cholesterol ester crystals and granulomas, pulmonary fibrosis, emphysema, and pneumothoraces. The available evidence suggests exposure to indium compounds causes a novel lung disease that may begin with PAP and progress to include fibrosis and emphysema, and, in some cases, premature death. Prospective studies are needed to better define the natural history and prognosis of this emerging lung disease and identify effective prevention strategies.
Topics: Adult; Biomarkers; Bronchoscopy; Diagnosis, Differential; Disease Progression; Humans; Indium; Lung Diseases; Male; Occupational Diseases; Occupational Exposure; Pancreatitis-Associated Proteins; Respiratory Function Tests; Risk Factors; Tomography, X-Ray Computed
PubMed: 22207675
DOI: 10.1378/chest.11-1880 -
American Journal of Industrial Medicine Jul 2016Workers manufacturing indium-tin oxide (ITO) are at risk of elevated indium concentration in blood and indium lung disease, but relationships between respirable indium...
BACKGROUND
Workers manufacturing indium-tin oxide (ITO) are at risk of elevated indium concentration in blood and indium lung disease, but relationships between respirable indium exposures and biomarkers of exposure and disease are unknown.
METHODS
For 87 (93%) current ITO workers, we determined correlations between respirable and plasma indium and evaluated associations between exposures and health outcomes.
RESULTS
Current respirable indium exposure ranged from 0.4 to 108 μg/m(3) and cumulative respirable indium exposure from 0.4 to 923 μg-yr/m(3) . Plasma indium better correlated with cumulative (rs = 0.77) than current exposure (rs = 0.54) overall and with tenure ≥1.9 years. Higher cumulative respirable indium exposures were associated with more dyspnea, lower spirometric parameters, and higher serum biomarkers of lung disease (KL-6 and SP-D), with significant effects starting at 22 μg-yr/m(3) , reached by 46% of participants.
CONCLUSIONS
Plasma indium concentration reflected cumulative respirable indium exposure, which was associated with clinical, functional, and serum biomarkers of lung disease. Am. J. Ind. Med. 59:522-531, 2016. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
Topics: Adult; Air Pollutants, Occupational; Biomarkers; Environmental Monitoring; Humans; Indium; Lung Diseases; Middle Aged; Occupational Exposure; Occupations; Spirometry; Tin Compounds
PubMed: 27219296
DOI: 10.1002/ajim.22585 -
Nano Letters Mar 2020Semiconductor quantum dots (QDs) are attractive fluorescent contrast agents for imaging due to their superior photophysical properties, but traditional QDs comprise...
Semiconductor quantum dots (QDs) are attractive fluorescent contrast agents for imaging due to their superior photophysical properties, but traditional QDs comprise toxic materials such as cadmium or lead. Copper indium sulfide (CuInS, CIS) QDs have been posited as a nontoxic and potentially clinically translatable alternative; however, previous studies utilized particles with a passivating zinc sulfide (ZnS) shell, limiting direct evidence of the biocompatibility of the underlying CIS. For the first time, we assess the biodistribution and toxicity of unshelled CIS and partially zinc-alloyed CISZ QDs in a murine model. We show that bare CIS QDs breakdown quickly, inducing significant toxicity as seen in organ weight, blood chemistry, and histology. CISZ demonstrates significant, but lower, toxicity compared to bare CIS, while our measurements of core/shell CIS/ZnS are consistent with literature reports of general biocompatibility. cytotoxicity is dose-dependent on the amount of metal released due to particle degradation, linking degradation to toxicity. These results challenge the assumption that removing heavy metals necessarily reduces toxicity: indeed, we find comparable cytotoxicity between CIS and CdSe QDs, while CIS caused severe toxicity compared to CdSe. In addition to highlighting the complexity of nanotoxicity and the differences between the and outcomes, these unexpected results serve as a reminder of the importance of assessing the biocompatibility of core QDs absent the protective ZnS shell when making specific claims of compositional biocompatibility.
Topics: Animals; Copper; Cytotoxins; Dose-Response Relationship, Drug; Female; Hep G2 Cells; Humans; Indium; Mice; Mice, Inbred BALB C; Quantum Dots; Sulfides
PubMed: 31999467
DOI: 10.1021/acs.nanolett.9b05259 -
Particle and Fibre Toxicology Dec 2022Many studies have shown that occupational exposure to indium and its compounds could induce lung disease. Although animal toxicological studies and human epidemiological...
BACKGROUND
Many studies have shown that occupational exposure to indium and its compounds could induce lung disease. Although animal toxicological studies and human epidemiological studies suggest indium exposure may cause lung injury, inflammation, pulmonary fibrosis, emphysema, pulmonary alveolar proteinosis, and even lung cancer, related data collected from humans is currently limited and confined to single workplaces, and the early effects of exposure on the lungs are not well understood.
OBJECTIVES
This study combined population studies and animal experiments to examine the links of indium with pulmonary injury, as well as its mechanism of action. A cross-sectional epidemiological study of indium-exposed workers from China was conducted to evaluate associations between occupational indium exposure and serum biomarkers of early effect. This study also compares and analyzes the causal perspectives of changes in human serum biomarkers induced by indium compound exposure and indium exposure-related rat lung pathobiology, and discusses possible avenues for their recognition and prevention.
METHODS
This is a study of 57 exposed (at least 6 h per day for one year) workers from an indium ingot production plant, and 63 controls. Indium concentration in serum, urine, and airborne as exposure indices were measured by inductively coupled plasma-mass spectrometry. Sixteen serum biomarkers of pulmonary injury, inflammation, and oxidative stress were measured using ELISA. The associations between serum indium and 16 serum biomarkers were analyzed to explore the mechanism of action of indium on pulmonary injury in indium-exposed workers. Animal experiments were conducted to measure inflammatory factors levels in bronchoalveolar lavage fluid (BALF) and lung tissue protein expressions in rats. Four different forms of indium compound-exposed rat models were established (intratracheal instillation twice per week, 8 week exposure, 8 week recovery). Model I: 0, 1.2, 3, and 6 mg/kg bw indium tin oxide group; Model II: 0, 1.2, 3, and 6 mg/kg bw indium oxide (InO) group; Model III: 0, 0.523, 1.046, and 2.614 mg/kg bw indium sulfate (In(SO)) group; Model IV: 0, 0.065, 0.65, and 1.3 mg/kg bw indium trichloride (InCl) group. Lung pathological changes were assessed by hematoxylin & eosin, periodic acid Schiff, and Masson's staining, transmission electron microscopy, and the protein changes were determined by immunohistochemistry.
RESULTS
In the production workshop, the airborne indium concentration was 78.4 μg/m. The levels of serum indium and urine indium in indium-exposed workers were 39.3 μg/L and 11.0 ng/g creatinine. Increased lung damage markers, oxidative stress markers, and inflammation markers were found in indium-exposed workers. Serum indium levels were statistically and positively associated with the serum levels of SP-A, IL-1β, IL-6 in indium-exposed workers. Among them, SP-A showed a duration-response pattern. The results of animal experiments showed that, with an increase in dosage, indium exposure significantly increased the levels of serum indium and lung indium, as well as the BALF levels of IL‑1β, IL‑6, IL‑10, and TNF‑α and up-regulated the protein expression of SP-A, SP-D, KL-6, GM-CSF, NF-κB p65, and HO-1 in all rat models groups. TEM revealed that In(SO) and InCl are soluble and that no particles were found in lung tissue, in contrast to the non-soluble compounds (ITO and InO). No PAS-staining positive substance was found in the lung tissue of In(SO) and InCl exposure groups, whereas ITO and InO rat models supported findings of pulmonary alveolar proteinosis and interstitial fibrosis seen in human indium lung disease. ITO and InCl can accelerate interstitial fibrosis. Findings from our in vivo studies demonstrated that intra-alveolar accumulation of surfactant (immunohistochemistry) and characteristic cholesterol clefts granulomas of indium lung disease (PAS staining) were triggered by a specific form of indium (ITO and InO).
CONCLUSIONS
In indium-exposed workers, biomarker findings indicated lung damage, oxidative stress and an inflammatory response. In rat models of the four forms of indium encountered in a workplace, the biomarkers response to all compounds overall corresponded to that in humans. In addition, pulmonary alveolar proteinosis was found following exposure to indium tin oxide and indium oxide in the rat models, and interstitial fibrosis was found following exposure to indium tin oxide and indium trichloride, supporting previous report of human disease. Serum SP-A levels were positively associated with indium exposure and may be considered a potential biomarker of exposure and effect in exposed workers.
Topics: Humans; Rats; Animals; Pulmonary Alveolar Proteinosis; Indium; Cross-Sectional Studies; Rodentia; Interleukin-6; Lung Injury; Pulmonary Fibrosis; Inflammation; Biomarkers
PubMed: 36539793
DOI: 10.1186/s12989-022-00510-w -
Scientific Reports Jul 2020Indium compounds have been widely used in manufacturing displays of mobile phones, computers and televisions. However, inhalation exposure to indium compounds causes...
Indium compounds have been widely used in manufacturing displays of mobile phones, computers and televisions. However, inhalation exposure to indium compounds causes interstitial pneumonia in exposed workers and lung cancer in experimental animals. 8-Nitroguanine (8-nitroG) is a mutagenic DNA lesion formed under inflammatory conditions and may participate in indium-induced carcinogenesis. In this study, we examined 8-nitroG formation in A549 cultured human lung epithelial cells treated with indium compounds, including nanoparticles of indium oxide (InO) and indium-tin oxide (ITO), and indium chloride (InCl). We performed fluorescent immunocytochemistry to examine 8-nitroG formation in indium-exposed A549 cells. All indium compounds significantly increased 8-nitroG formation in A549 cells at 5 ng/ml after 4 h incubation. 8-NitroG formation was largely reduced by 1400 W, methyl-β-cyclodextrin (MBCD) and monodansylcadaverine (MDC), suggesting the involvement of nitric oxide synthase and endocytosis. 8-NitroG formation in A549 cells was also largely suppressed by small interfering RNA (siRNA) for high-mobility group box-1 (HMGB1), receptor for advanced glycation and end products (AGER, RAGE) and Toll-like receptor 9 (TLR9). These results suggest that indium compounds induce inflammation-mediated DNA damage in lung epithelial cells via the HMGB1-RAGE-TLR9 pathway. This mechanism may contribute to indium-induced genotoxicity in the respiratory system.
Topics: A549 Cells; Antigens, Neoplasm; DNA Damage; Guanine; HMGB1 Protein; Humans; Indium; Lung Neoplasms; Mitogen-Activated Protein Kinases; Mutagens; Nanoparticles; Toll-Like Receptor 9
PubMed: 32612147
DOI: 10.1038/s41598-020-67488-3 -
Nanomedicine : Nanotechnology, Biology,... Nov 2018Quantum dot (QD) nanoparticles are highly promising contrast agents and probes for biomedical applications owing to their excellent photophysical properties. However,...
Quantum dot (QD) nanoparticles are highly promising contrast agents and probes for biomedical applications owing to their excellent photophysical properties. However, toxicity concerns about commonly used cadmium-based QDs hinder their translation to clinical applications. In this study we describe the in vivo biodistribution and toxicology of indium-based water soluble QDs in rats following intravenous administration. The biodistribution measured at up to 90 days showed that QDs mainly accumulated in the liver and spleen, with similar elimination kinetics to subcutaneous administration. Evidence for QD degradation in the liver was found by comparing photoluminescence measurements versus elemental analysis. No organ damage or histopathological lesions were observed for the QDs treated rats after 24 h, 1 and 4 weeks following intravenous administration at 12.5 mg/kg or 50 mg/kg. Analysis of serum biochemistry and complete blood counts found no toxicity. This work supports the strong potential of indium-based QDs for translation into the clinic.
Topics: Animals; Cadmium; Female; Indium; Liver; Models, Animal; Nanoparticles; Quantum Dots; Rats; Tissue Distribution; Toxicity Tests
PubMed: 30048815
DOI: 10.1016/j.nano.2018.07.009 -
Molecules (Basel, Switzerland) Feb 2023The chemical industry still requires development of environmentally friendly processes. Acid-catalysed chemical processes may cause environmental problems. Urgent need... (Review)
Review
The chemical industry still requires development of environmentally friendly processes. Acid-catalysed chemical processes may cause environmental problems. Urgent need to replace conventional acids has forced the search for sustainable alternatives. Metal-containing ionic liquids have drawn considerable attention from scientists for many years. These compounds may exhibit very high Lewis acidity, which is usually dependent on the composition of the ionic liquid with the particular content of metal salt. Therefore, metal-containing ionic liquids have found a lot of applications and are successfully employed as catalysts, co-catalysts or reaction media in various fields of chemistry, especially in organic chemistry. Gallium(III)- and indium(III)-containing ionic liquids help to transfer the remarkable activity of metal salts into even more active and easier-to-handle forms of ionic liquids. This review highlights the wide range of possible applications and the high potential of metal-containing ionic liquids with special focus on Ga(III) and In(III), which may help to outline the framework for further development of the presented research topic and synthesis of new representatives of this group of compounds.
Topics: Ionic Liquids; Indium; Gallium; Lewis Acids; Chemistry Techniques, Synthetic
PubMed: 36838943
DOI: 10.3390/molecules28041955 -
Journal of Occupational Health 2011Two- and 13-week inhalation toxicities of indium-tin oxide (ITO) and indium oxide (IO) were characterized for risk assessments of workers exposed to ITO. (Comparative Study)
Comparative Study
OBJECTIVES
Two- and 13-week inhalation toxicities of indium-tin oxide (ITO) and indium oxide (IO) were characterized for risk assessments of workers exposed to ITO.
METHODS
F344 rats of both sexes were exposed by inhalation to ITO or IO aerosol for 6 h/day, 5 day/wk for 2 wk at 0, 0.1, 1, 10 or 100 mg/m(3) or 13 wk at 0, 0.1 or 1 mg/m(3). An aerosol generator and inhalation exposure system was constructed.
RESULTS
Blood and lung contents of indium were elevated in a dose-related manner in the ITO- and IO-exposed rats. ITO and IO particles were deposited in the lung, mediastinal lymph node and nasal-associated lymphoid tissue. Exposures to ITO and IO induced alveolar proteinosis, infiltrations of alveolar macrophages and inflammatory cells and alveolar epithelial hyperplasia in addition to increased lung weight. ITO affected the lung more severely than IO did. Fibrosis of alveolar wall developed and some of these lesions worsened at the end of the 26-week post-exposure period.
CONCLUSIONS
Persistent pulmonary lesions including alveolar proteinosis and macrophage infiltration occurred after 2- and 13-week inhalation exposures of rats to ITO and IO. Fibrosis of alveolar wall developed later. These lesions occurred after ITO exposure at the same concentration as the current occupational exposure limit in the USA and at blood indium levels below the biological exposure index in Japan for indium.
Topics: Administration, Inhalation; Animals; Female; Indium; Inhalation Exposure; Macrophages, Alveolar; Male; Pulmonary Alveolar Proteinosis; Pulmonary Fibrosis; Rats; Rats, Inbred F344; Time Factors; Tin Compounds
PubMed: 21233592
DOI: 10.1539/joh.l10128 -
Occupational and Environmental Medicine Aug 2022To determine whether engineering controls and respiratory protection had measurable short-term impact on indium exposure and respiratory health among current indium-tin...
Two-year follow-up of exposure, engineering controls, respiratory protection and respiratory health among workers at an indium-tin oxide (ITO) production and reclamation facility.
OBJECTIVES
To determine whether engineering controls and respiratory protection had measurable short-term impact on indium exposure and respiratory health among current indium-tin oxide production and reclamation facility workers.
METHODS
We documented engineering controls implemented following our 2012 evaluation and recorded respirator use in 2012 and 2014. We measured respirable indium (In) and plasma indium (In) in 2012 and 2014, and calculated change in In (∆In) and In (∆In) by the 13 departments. We assessed symptoms, lung function, serum biomarkers of interstitial lung disease (Krebs von den Lungen (KL)-6 and surfactant protein (SP)-D) and chest high-resolution CT at both time points and evaluated workers who participated in both 2012 and 2014 for changes in health outcomes (new, worsened or improved).
RESULTS
Engineering controls included installation of local exhaust ventilation in both grinding departments (Rotary and Planar) and isolation of the Reclaim department. Respiratory protection increased in most (77%) departments. ∆In and ∆In often changed in parallel by department. Among 62 workers participating in both 2012 and 2014, 18 (29%) had new or worsening chest symptoms and 2 (3%) had functional decline in lung function or radiographic progression, but average KL-6 and SP-D concentrations decreased, and no cases of clinical indium lung disease were recognised.
CONCLUSIONS
Increased engineering controls and respiratory protection can lead to decreased In, In and biomarkers of interstitial lung disease among workers in 2 years. Ongoing medical monitoring of indium-exposed workers to confirm the longer-term effectiveness of preventive measures is warranted.
Topics: Biomarkers; Follow-Up Studies; Humans; Indium; Lung Diseases, Interstitial; Occupational Exposure; Pulmonary Surfactant-Associated Protein D; Tin Compounds
PubMed: 35414568
DOI: 10.1136/oemed-2021-107897