Evaluation of Risk and Uncertainty for Model-Predicted NOAELs of Engineered Nanomaterials Based on Dose-Response-Recovery Clusters

Details

• Personal Author:
  Gernand JM ; Ramchandran V
• Description:
  Experimental toxicology studies for the purposes of setting occupational exposure limits for aerosols have drawbacks including excessive time and cost which could be overcome or limited by the development of computational approaches. A quantitative, analytical relationship between the characteristics of emerging nanomaterials and related in vivo toxicity can be utilized to better assist in the subsequent mitigation of exposure toxicity by design. Predictive toxicity models can be used to categorize and define exposure limitations for emerging nanomaterials. Model-based no-observed-adverse-effect-level (NOAEL) predictions were derived for toxicologically distinct nanomaterial clusters, referred to as model-predicted no observed adverse effect levels (MP-NOAELs). The lowest range of MP-NOAELs for the polymorphonuclear neutrophil (PMN) response observed by carbon nanotubes (CNTs) was found to be 21-35 µg/kg (cluster "A"), indicating that the CNT belonging to cluster A showed the earliest signs of adverse effects. Only 25% of the MP-NOAEL values for the CNTs can be quantitatively defined at present. The lowest observed MP-NOAEL range for the metal oxide nanoparticles was Cobalt oxide nanoparticles (cluster III) for the macrophage (MAC) response at 54-189 µg/kg. Nearly 50% of the derived MP-NOAEL values for the metal oxide nanoparticles can be quantitatively defined based on current data. A sensitivity analysis of the MP-NOAEL derivation highlighted the dependency of the process on the shape and type of the fitted dose-response model, its parameters, dose selection and spacing, and the sample size analyzed. [Description provided by NIOSH]
• Subjects:
  Aerosols Occupational Exposure Occupational Health Safety Toxicology
• Keywords:
  Aerosol Particles Author Keywords: Dose-response Carbon Nanotubes CNT CNTs Dose Response Hierarchical Clustering Metal Oxides Nanomaterials Nanoparticles NOAEL Occupational Exposure Potency Pulmonary Toxicity Recovery Risk Assessment

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• ISSN:
  2332-9017
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; Pennsylvania
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  9
• Issue:
  1
• NIOSHTIC Number:
  nn:20067780
• Citation:
  ASME J Risk Uncertainty Part B 2023 Mar; 9(1):011205
• Contact Point Address:
  Jeremy M. Gernand, Department of Energy and Mineral Engineering, Pennsylvania State University, University Park, PA 16802
• Email:
  jmgernand@psu.edu
• Federal Fiscal Year:
  2023
• Performing Organization:
  Pennsylvania State University
• Peer Reviewed:
  True
• Start Date:
  20150901
• Source Full Name:
  ASCE-ASME Journal of Risk and Uncertainty in Engineering Systems, Part B. Mechanical Engineering
• End Date:
  20180601
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:fb5d09fb069a7ae93bd67557bdbe4aa35f7d9cdded12a7efbe5a37263e90388f0b458dabd9ed708681bc90015a26071a8d81ad44a89d9a47ea0fe261157b6f9f
• Download URL:
  https://stacks.cdc.gov/view/cdc/230039/cdc_230039_DS1.pdf
• File Type:
  [PDF - 1.22 MB ]