Instillation of indium-tin oxide production facility particles in rats induces pulmonary toxicity

Details

• Personal Author:
  Badding M ; Barger M ; Cummings, Kristin J. ; Dunnick K ; Fix N ; Leonard, Stephanie ; Orandle M
• Description:
  Indium-tin oxide (ITO) is a mixture of metal oxides and is used to make transparent conductive coatings for touch-screen and liquid crystal display electronics. As the demand for consumer electronics continues to rise, concern over occupational exposures to potentially toxic particles generated during ITO production has increased. Epidemiologic studies have shown an association between workers exposed to ITO and development of pulmonary alveolar proteinosis (PAP) and fibrotic interstitial lung disease. Our previous in vitro studies have demonstrated cytotoxicity and inflammasome activation in response to various indium-containing particles. However, which of these indium materials or specific industrial processes may be the most toxic in vivo remains unknown. In the current study, particle samples were collected at different production stages throughout an ITO facility and various endpoints were evaluated over a time course following rat pulmonary exposures to these particles. Indium oxide (In2O3) is a starting material, sintered ITO (SITO) is generated during the grinding of the final ITO product, and ventilation dust (VD) is present during reclamation of indium from left-over materials (and therefore, contains SITO). Rats were exposed via a single intratracheal instillation dose of 0 mg (PBS vehicle control), 0.5 mg (VD only), 1 mg, or 5 mg per rat (n = 6-8/group). Each particle type induced pulmonary inflammation and damage in rats (evaluated at 1, 7, and 90 days post-instillation), but SITO and VD caused the most damage when responses at the same dose were compared on days 7 and 90. SITO and VD also led to significantly higher plasma indium levels than In2O3. Downstream pathological changes such as PAP and fibrosis were observed in response to all three particles 90 days post-treatment, with a trend towards greatest severity in animals exposed to VD when comparing animals that received the same dose. These findings may inform workplace exposure reduction efforts and provide a better understanding of the pathogenesis of this emerging occupational health issue. [Description provided by NIOSH]
• Subjects:
  Dust Electrical Equipment And Supplies Environmental Monitoring Fibrosis Hazardous Substances Immune System Indium Laboratories Lung Lung Diseases Metals Occupational Health Particulate Matter Respiratory System Respiratory Tract Diseases Safety Toxicology

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• Keywords:
  Alveolar Cells Coatings Dose Response Dust Particles Electronic Components Exposure-assessment Immune Reaction Indium Compounds Industrial Processes Intestinal Cells In Vivo Study Laboratory Animals Laboratory Testing Lung-disease Lung-fibrosis Metal-compounds Metal Oxides Oxides Particulates Pathogenesis Pulmonary Function Pulmonary System Disorders Respiratory-system-disorders Sampling Tin Tin Oxides Toxic Effects Toxic Materials

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Louisiana ; New York ; North Carolina ; OSHA Region 2 ; OSHA Region 3 ; OSHA Region 4 ; OSHA Region 6 ; Virginia ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division ; RHD - Respiratory Health Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  74
• Volume:
  150
• Issue:
  1
• NIOSHTIC Number:
  nn:20047613
• Citation:
  Toxicologist 2016 Mar; 150(1):74
• CAS Registry Number:
  Indium tin oxide (In1.69Sn0.15O2.85) (CAS RN 71243-84-0)
• Federal Fiscal Year:
  2016
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 55th Annual Meeting and ToxExpo, March 13-17, 2016, New Orleans, Louisiana
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:a8f6f4e15215827e374d4a63afd485f99639356dd265c84fbf665c111725e4fe8aceb1af725516a750c3772f9ffc10d6aa43935392d68d3cd0144ff65471597b
• Download URL:
  https://stacks.cdc.gov/view/cdc/202628/cdc_202628_DS1.pdf
• File Type:
  [PDF - 441.30 KB ]