In Vitro Toxicity Assessment of Pre- and Post-Incinerated Organomodified Nanoclays on Airway Epithelial and Lung Fibroblast Cells

Details

• Journal Article:
  Chemical Research in Toxicology
• Personal Author:
  Stueckle, Todd A. ; Jensen, Jake ; Coyle, Jayme P. ; Wagner, Alixandra ; Derk, Raymond C. ; Kornberg, Tiffany G. ; Friend, Sherri A. ; Schreiner, Molly ; Ufelle, Alexander C. ; Agarwal, Sushant ; Gupta, Rakesh K. ; Dinu, Cerasela Z. ; Rojanasakul, Liying W.
• Description:
  The use of two-dimensional organomodified nanoclays (ONCs) to improve nanocomposite properties continues to grow. Recent evidence suggests that airborne nanoclays in occupational environments pose an inhalation hazard; however, health risks and the underlying mechanisms remain undefined. In vivo studies evaluating pre- and post-incinerated ONC exposures found that cytotoxicity, inflammation, and fibrotic signaling responses are coating- and incineration status-dependent. We hypothesized that physicochemical property differences associated with coating presence/absence and incineration status of nanoclays will elicit changes in key events (KE) in exposed human small airway epithelial (SAECs) and normal lung fibroblast (NHLF) cells that contribute to pulmonary lung fibrosis. Using multiplex high-throughput screening strategies, SAEC and NHLF cells were acutely exposed (0-20 µg/cm2) to pristine nanoclay (CloisNa), an ONC (Clois30B), their incinerated byproducts (I-CloisNa and I-Clois30B), and crystalline silica (CS), to evaluate how ONC characteristics influence several KE in the pulmonary fibrosis adverse outcome pathway. In vitro exposure to pre-incinerated nanoclay induced organic coating-dependent cytotoxicity in SAECs. CloisNa caused disruption of mitochondrial membrane potential, which coincided with loss in viability in both cell types. Clois30B exposure caused dose-dependent SAEC cytotoxicity, micronuclei formation, and mitochondrial hyperpolarization in SAECs and NHLFs. Incinerated nanoclays were noncytotoxic but elicited a SAEC mitochondrial radical and pro-inflammatory response. Direct in vitro exposure to NHLFs exhibited particle-dependent increased live cell count, reactive oxygen species production, and a-smooth muscle actin expression. Nanoclay-exposed NHLFs (0.6 µg/cm2) possessed elevated collagen I levels while the same mass dose in vivo (300 µg/lung) favored elevated fibronectin and collagen III deposition for CloisNa and CS. In conclusion, organic coating presence and incineration status influenced nanoclays' effects on cellular interaction, membrane integrity, inflammation, fibroblast activation, and collagen accumulation in exposed cell models. Although pre-incinerated nanoclay exposure promoted collagen accumulation in vitro, it was a poor predictor of in vivo model reticular fiber deposition.
• Subjects:
  Lung Occupational Health Particulate Matter Safety
• Keywords:
  Nanoclays; Airborne particulates; Immune reaction; Macrophages; Cytotoxic effects; Coatings; In vitro study; Toxicology; Lung fibrosis; Nanocomposites
• Source:
  Chem Res Toxicol 2025 Oct; 38(10):1708-1728
• ISSN:
  0893-228X
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  West Virginia ; Pennsylvania ; Philadelphia Region [OSHA]
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  21 pdf pages
• Volume:
  38
• NIOSHTIC Number:
  nn:20071274
• Contact Point Address:
  Todd A. Stueckle, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, United States
• Email:
  jux5@cdc.gov
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2026
• Peer Reviewed:
  True
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:46c7a07f1c8f34ca9a0ddb80ead237283f9229080e51efe10a8b20742efde113320b3ef9843e9cb24de41ecf77cbf671e211e0c75022b009790d58d003f76c81
• Download URL:
  https://stacks.cdc.gov/view/cdc/258751/cdc_258751_DS1.pdf
• File Type:
  [PDF - 10.67 MB ]