Integrated In Vitro-In Vivo Models for Nanomaterial and Ultrafine Particle Toxicity Testing: Moving from a Screening Hazard Tool to Predictive Models for In Vivo Adverse Effects

Details

• Personal Author:
  Davidson DC ; Kodali V ; Kornberg T ; Rojanasakul LW ; Rojanasakul Y ; Stueckle, Todd A.
• Description:
  Engineered nanomaterial and ultrafine materials (ENMs) are revolutionizing a diverse spectrum of commercial and industrial sectors with improved or novel technologies. Animal inhalation studies report ENM deposition in the deep lung with distinct disease risks; however, they are time- and resource- consuming and cannot be used to assess each ENM. With the large diversity and complicated life cycles of ENMs, there is no consensus on how to rapidly screen associated hazards and define risks for occupational and public exposures. Several regulatory bodies have urged researchers to develop alternative approaches and integrated in vitro-in vivo effect models to press the question: Can in vitro models predict in vivo effects? Here, we examine several in vitro models that show evidence for predictability of in vivo damage, fibrosis, and tumorigenesis responses using scaled, realistic pulmonary exposure doses for several ENMs. Single- and multi-walled carbon nanotubes (CNT), and cerium oxide are known to penetrate into lung interstitium and induce interstitial fibrosis. Using scaled mass dose per alveolar surface area, these ENMs stimulate fibroblast proliferation, collagen production, and a fibroblast stem cell-like phenotype that correlate with in vivo effects. Furthermore, the use of co-culture models has improved the understanding of how the inflammatory response mediates fibrosis development. Since some CNTs possess properties similar to known carcinogens, long term, continuous exposures were tested in vitro and resulted in neoplastic or malignant transformation that correlated well with in vivo effect. CNT-transformed human lung bronchial epithelial cells exhibited elevated cancer hallmarks, proto-oncogene signaling, and evidence of cancer stem-like cells, consistent with known lung cancer signaling and established clinical biomarkers. Recent expansion of this approach to nano-sized metal oxides suggested that in vitro human cell models have potential as a useful tumorigenesis screening tool. In summary, development of integrated in vitro-in vivo approaches to assess ENM and ultrafine particle toxicity will fill key knowledge gaps and allow development of predictive in vitro models. [Description provided by NIOSH]
• Subjects:
  Animals Biomarkers Carcinogens Environmental Exposure Hazardous Substances Immune System Laboratories Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety Toxicology

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• Keywords:
  Analytical Models Cancer Carbon Nanotubes Carcinogenesis Cerium Oxides Exposure Assessment Exposure Levels Fibroblasts Health Effects Health Hazards Immune Reaction Inhalation In Vitro Study In Vivo Study Laboratory Animals Laboratory Testing Lung Cells Lung Fibrosis Medical Screening Multi-walled Carbon Nanotubes MWCNT Nanomaterials Nanotechnology Nanotoxicology Oncogenic Agents Pulmonary Effects Screening Methods Single-walled Carbon Nanotubes SWCNT Toxic Effects Tumorigenesis Ultrafine Particles

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; OSHA Region 6 ; Texas ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  162
• Issue:
  1
• NIOSHTIC Number:
  nn:20051173
• Citation:
  Toxicologist 2018 Mar; 162(1):163
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6) ; Ceria (CAS RN 1306-38-3)
• Federal Fiscal Year:
  2018
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 57th Annual Meeting and ToxExpo, March 11-15, 2018, San Antonio, Texas
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:5d9a3c76595f05344357749b098e7918a6408d5dcc0a923b0fcc851db8957cbe9b78efce3e58701f857e7d5885859bd656fd62951bbae4599eb2b8db0fc0018f
• Download URL:
  https://stacks.cdc.gov/view/cdc/211265/cdc_211265_DS1.pdf
• File Type:
  [PDF - 838.69 KB ]