Multimodal Mass Spectromtry Analysis Following Repeated Intratracheal Instillation of Dispersed Silver Nanoparticles in Rats

Details

• Personal Author:
  Antonini J ; Boyce GR ; Friend S ; Kashon M ; Roberts, Jennifer R. ; Stefaniak, Aleksandr B.
• Description:
  Silver nanoparticles are among the most widely manufactured nanomaterials and have been incorporated into a wide variety of consumer products such as textiles, detergents, medical devices, drug delivery products, anti-microbial sprays, personal care products, paints/coatings, and water purification. This has led to the potential increase in risk of worker exposure to these particles. We have previously conducted an in vivo study to characterize pulmonary and systemic effects following repeated exposure where rats were intratracheally instilled once a week for eight weeks with 9.35 microg or 112 microg of dispersed silver nanoparticles (Nano-Ag) or dispersion medium (DM) as a vehicle control. Lung histopathology, and analyses of bronchoalveolar lavage fluid (BALF) and serum were performed at 7, 28, and 84 days after the last exposure. Lung injury was characterized by alveolar and interstitial inflammation, as well as oxidative stress. In the current study, a metabolomic approach was employed to characterized changes in the BALF and serum to further examine mechanisms of toxicity and establish a potential panel of biomarkers of exposure and effect. Metabolite characterization was conducted with matrix assisted laser desorption ionization (MALDI) and liquid chromatography mass spectrometry (LC-MS). The metabolomics analysis revealed a significant increase in 44 metabolites in BALF, including 1,2-Dipalmitoyl-sn-glycero-3-phosphoglycerol (DPPG) and cholesterol in the rats exposed to 112 microg at the 7- and 28-day time points. Rats exposed to the high dose had a significant increase in approx. 60 serum metabolites, with the greatest degree of change in the alanine biosynthesis pathway intermediates in the serum, which have been shown to be indicators of liver toxicity. There was a >2.0-fold increase in alanine, valine, and glutamate in the 112 microg exposed animals at the 7- and 28-day time points. The results of this study show that pulmonary exposure to nanosilver particles leads to changes in the BALF lipidome, which may be related to the pathway of lung injury and oxidative stress. In addition, increased levels of circulating metabolites indicative of liver toxicity agree with numerous in vivo studies by other investigators. Further analysis of these molecules and lipids will be conducted to establish a potential biomarker panel for nanosilver exposure and effect. [Description provided by NIOSH]
• Subjects:
  Biomarkers Blood Energy Metabolism Environmental Exposure Laboratories Lipids Lung Occupational Health Respiratory System Safety Silver Toxicology

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• Keywords:
  Amino Acids Analytical Instruments Biosynthesis Blood Serum Desorption Exposure Assessment Exposure Levels Ionization Laboratory Animals Laboratory Testing Lasers Liquid Chromatography Liver Damage Mass Spectrometry Metabolites Nanoparticles Nanotechnology Nanotoxicology Oxidative Stress Pulmonary Effects Serological Techniques Serology Serum Cholesterol Silver Compounds Toxic Effects

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; OSHA Region 3 ; OSHA Region 9 ; 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:
  39-40
• Volume:
  174
• Issue:
  1
• NIOSHTIC Number:
  nn:20058853
• Citation:
  Toxicologist 2020 Mar; 174(1):39-40
• CAS Registry Number:
  Dipalmitoylphosphatidylglycerol (CAS RN 4537-77-3) ; Glutamate(1-) (CAS RN 11070-68-1) ; L-Alanine (CAS RN 56-41-7) ; L-Valine (CAS RN 72-18-4) ; Silver (CAS RN 7440-22-4)
• Federal Fiscal Year:
  2020
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 59th Annual Meeting and ToxExpo, March 15-19, 2020, Anaheim, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:0fff0cb04640dae7b79fee1ee89870d36b30c9fefc25a0ec6b97d495889ffedcb1ab73bec064cd120957ad74cd68008b29d84fbb9832617665a67fa19b0ef234
• Download URL:
  https://stacks.cdc.gov/view/cdc/223238/cdc_223238_DS1.pdf
• File Type:
  [PDF - 538.49 KB ]