Surface Area- and Mass-Based Comparison of Lung Toxicity and Allergic Exacerbation in an Ovalbumin Asthma Model Following Pulmonary Exposure to Fine and Ultrafine Nickel Oxide

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• Personal Author:
  Anderson, Stacey E. ; Roach KA ; Roberts, Jennifer R. ; Schwegler-Berry D ; Shane HL ; Stefaniak, Aleksandr B.
• Description:
  The correlation of specific nanomaterial physico-chemical properties with toxicological responses is an area of growing interest with implications for the selection of appropriate dose metrics in nanotoxicity studies. In this study, the role of nickel oxide mass and surface area in the induction of pulmonary inflammation and exacerbation of respiratory allergy was explored. To address this concept, 181 nm fine (NiO) and 42 nm ultrafine (NiONP) particles were characterized and incorporated into an in vivo time course study and ovalbumin (OVA) asthma model. Particle toxicity was compared at equal masses of 40 micrograms and at equal surface areas of 1.92 mm2. For the time course study, female BALB/c mice were exposed once to particles or vehicle control by oropharygenal aspiration and euthanized 1, 10, 19, or 29 d post-exposure, which represent critical time points in the OVA model. For the OVA model, mice were aspirated with particles on d 0, sensitized to OVA via IP injection on d 1 and 10, challenged with OVA by aspiration on d 19 and 28, and euthanized on d 29. In the time course study, exposure to mass-normalized doses of particles resulted in significantly elevated lactate dehydrogenase levels, lung neutrophil number, and mediastinal lymph node size in mice exposed to NiONP, which persisted to 29 d post-exposure. However, normalization of doses for surface area mitigated all differences between particles, suggesting that NiO surface area drives pulmonary inflammation. In the OVA model, exposure to equal masses of NiO and NiONP induced differential mechanisms of immune augmentation. Exposure to NiO caused increased penh over allergy controls and higher levels of Th2 cytokines in the lavage fluid. Exposure to NiONP resulted in significantly increased lymph node size over all other groups and elevated levels of both Th1 and Th2 cytokines over control animals, but reduced serum OVA IgE levels. Interestingly, normalization of doses for surface area in the OVA model mitigated differences in serum IgE and Th2 cytokine levels, but not eosinophil influx to the lung and Th1 cytokines. Overall, findings suggest that although surface area of NiO dictates pulmonary injury and inflammation, it may not be the only physico-chemical property responsible for modulation of immune responses in the lung. [Description provided by NIOSH]
• Subjects:
  Albumins Asthma Asthma, Occupational Body Fluids Chemistry Environmental Exposure Hypersensitivity Immune System Laboratories Lung Lymphatic System Occupational Health Particulate Matter Respiratory System Safety Toxicology

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• Keywords:
  Albumin Allergic Reactions Allergies Analytical Models Body Fluids Chemical Properties Dose Response Exposure Assessment Exposure Levels Immune Reaction Immunoglobulins Laboratory Animals Laboratory Testing Lung Burden Lymph Nodes Models Nanomaterials Nanotechnology Nanotoxicology Neutrophils Nickel Oxide Particle Size Particulates Physical Properties Pulmonary Effects Respiratory Irritants Surface Properties Toxic Effects 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 ; RHD - Respiratory Health Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  162
• Issue:
  1
• NIOSHTIC Number:
  nn:20051256
• Citation:
  Toxicologist 2018 Mar; 162(1):418
• CAS Registry Number:
  Nickel monoxide (CAS RN 1313-99-1)
• Federal Fiscal Year:
  2018
• NORA Priority Area:
  Construction ; 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:cdbd64b57cd190c18e600c8f2cd8705faf9f00fa477ad27e432c2c320cebfeb1ce12e04fc1f3d009eceb377106449f6c08c27f0d6e50db1b4315f0c1fa3ffdaa
• Download URL:
  https://stacks.cdc.gov/view/cdc/211318/cdc_211318_DS1.pdf
• File Type:
  [PDF - 855.14 KB ]