Translating nanoparticle dosimetry from conventional in vitro systems to occupational inhalation exposures

Details

• Alternative Title:
  J Aerosol Sci
• Personal Author:
  Smith, Jordan Ned ; Skinner, Andrew W.
• Description:
  As encouraged by |st |, researchers increasingly apply high-throughput | approaches to identify and characterize nanoparticle hazards, including conventional aqueous cell culture systems to assess respiratory hazards. Translating nanoparticle dose from conventional toxicity testing systems to relevant human exposures remains a major challenge for assessing occupational risk of nanoparticle exposures. Here, we explored existing computational tools and data available to translate nanoparticle dose metrics from cellular test systems to inhalation exposures of silver nanoparticles in humans. We used the Multiple-Path Particle Dosimetry (MPPD) Model to predict nanoparticle deposition of humans exposed to 20 and 110 nm silver nanoparticles at 0.9 μg/m| over an 8 h period, the proposed National Institute of Occupational Safety and Health (NIOSH) recommended exposure limit (REL). MPPD predicts 8.1 and 3.7 μg of silver deposited in an 8 h period for 20 and 110 nm nanoparticles, respectively, with 20 nm particles displaying nearly 11-fold higher total surface area deposited. Peak deposited nanoparticle concentrations occurred more proximal in the pulmonary tract compared to mass deposition patterns (generation 4 vs. generations 20-21, respectively) due to regional differences in lung lining fluid volumes. Assuming 0.4% nanoparticle dissolution by mass measured in previous studies predicted peak concentrations of silver ions in cells of 1.06 and 0.89 μg/mL for 20 and 110 nm particles, respectively. Both predicted concentrations are below the measured toxic threshold of 1.7 μg/mL of silver ions in cells from | assessments. Assuming 4% dissolution by mass predicted 10-fold higher silver concentrations in tissues, peaking at 10.6 and 8.9 μg/mL, for 20 and 110 nm nanoparticles respectively, exceeding the observed | toxic threshold and highlighting the importance and sensitivity of dissolution rates. Overall, this approach offers a framework for extrapolating nanotoxicity results from | cell culture systems to human exposures. Aligning appropriate dose metrics from | and | hazard characterizations and human pulmonary doses from occupational exposures are critical components for successful nanoparticle risk assessment and worker protection providing guidance for designing future | studies aimed at relevant human exposures.
• Subjects:
  Article Dose Metrics Dosimetry Modeling In Vitro To In Vivo Extrapolation Nanoparticle
• Source:
  J Aerosol Sci. 155
• Pubmed ID:
  35979194
• Pubmed Central ID:
  PMC9380399
• Document Type:
  Journal Article
• Funding:
  R01 OH011023/OH/NIOSH CDC HHSUnited States/
• Volume:
  155
• NIOSHTIC Number:
  nn:20065169
• Collection(s):
  CDC Public Access National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d0d584bbf8705f20a835c673ca1562d41138286e81aac68ea673c155c627519a3d30cce4541b5008cba40e0422dcd73904034fa7515497d239c1a9e3daeab6c7
• Download URL:
  https://stacks.cdc.gov/view/cdc/120416/cdc_120416_DS1.pdf
• File Type:
  [PDF - 527.15 KB ]