Evaluation of the Skin Sensitizing Potential of Gold Nanomaterials and the Impact of Established Dermal Sensitivity to Gold on the Pulmonary Immune Response with Respect to Dose Mass and Surface Area

Details

• Personal Author:
  Anderson, Stacey E. ; Roach KA ; Roberts, Jennifer R. ; Shane HL ; Stefaniak, Aleksandr B.
• Description:
  The easily-manipulated physico-chemical properties of gold nanomaterials (AuNM) have proven useful in many biomedical applications. However, the historical use of gold for the treatment of rheumatoid arthritis and the known sensitizing capacity of gold salts suggest that AuNM may exhibit immunomodulatory properties. To address this, three studies were performed using female C57BL/6 mice. First, the skin sensitizing capacity of different forms of gold was assessed in the Local Lymph Node Assay (LLNA) using soluble gold salt (AuCl, 10%) and increasing concentrations (2.5, 5, 10%) of gold particles (Au, 12.1 um) and spherical AuNM (30 nm). Next, the pulmonary immune effects of AuNM (10, 30, or 90 ug) were assessed 1 d, 4 d, and 8 d post-aspiration. Finally, the impact of existing dermal sensitivity to gold on the pulmonary immune response to different forms of gold was assessed. Mice were dermally sensitized to gold by three dermal exposures (1 d, 2 d, 3 d) to 10% AuCl or vehicle control (VC). Mice were then aspirated once (10 d), twice (10 and 14 d), or three times (10, 14, and 18 d) with VC, 30 ug Au, or a dose of AuNM normalized to the mass or surface area of the 30 ug Au (30 ug or 0.2 ug, respectively) and euthanized 1 d later. In the LLNA study, AuCl had a stimulation index (SI) of 10.9, in accordance with its known potent sensitizing capacity. Although the SI of AuNM (2.3) was higher than that of Au (1.1), a three-fold increase in lymphocyte proliferation was not observed for either particle, indicating minimal risk for dermal sensitization. In the dose-response study, AuNM induced only minimal lung injury and inflammation. However, exposure to the 90 ug dose did induce a significant increase in total number and percent activated CD4+ T-cells and B-cells in the mediastinal lymph nodes at 4 and 8 d. In the allergy study, after two and three aspirations, mice sensitized to gold exhibited elevated lung lymphocyte numbers which correlated to dose surface area. Moreover, serum IgE levels were significantly increased only in dermally-sensitized mice aspirated with AuNM, irrespective of dose, indicating a potential for increased susceptibility to the development of an IgE-mediated adaptive immune response following respiratory exposure. Collectively, the results from these studies suggest existing dermal sensitivity to gold may exacerbate the pulmonary immune effects resulting from AuNM inhalation. [Description provided by NIOSH]
• Subjects:
  Biological Assay Blood Chemistry Environmental Exposure Immune System Laboratories Lung Lymphatic System Occupational Health Respiratory System Safety Skin Toxicology

  More +
• Keywords:
  Bioassays Cell Function Cellular Effects Cellular Reactions Chemical Properties Dermal Exposures Dose Response Exposure Assessment Exposure Levels Gold Immune Reaction Immunochemistry Immunoglobulins Immunological Tests Inhalation Laboratory Animals Laboratory Testing Lymph Nodes Lymphocytes Nanomaterials Nanotechnology Nanotoxicology Physical Properties Pulmonary Effects Pulmonary System Sensitizers Skin Tests Sodium Compounds Sulfonates

  More +
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Maryland ; OSHA Region 3 ; 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:
  168
• Issue:
  1
• NIOSHTIC Number:
  nn:20055010
• Citation:
  Toxicologist 2019 Mar; 168(1):288
• CAS Registry Number:
  Gold (CAS RN 7440-57-5) ; Sodium anthraquinone-1-sulfonate (CAS RN 128-56-3)
• Federal Fiscal Year:
  2019
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 58th Annual Meeting and ToxExpo, March 10-14, 2019, Baltimore, Maryland
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:89baf9c65059a6450d5040b2ce0809891a0f0c73e271c7498c08b232454af888cba17d4747587f3853d6033453637ecfc483ac92f2d0bb9c2c6b33106cd3e087
• Download URL:
  https://stacks.cdc.gov/view/cdc/217414/cdc_217414_DS1.pdf
• File Type:
  [PDF - 859.99 KB ]