Inhalation of ortho-phthalaldehyde vapor causes systemic sensitization and allergic inflammation in the lymph nodes, nasal mucosa, and lung of mice

Details

• Personal Author:
  Fluharty K ; Johnson VJ ; Reynolds JS ; Wang W ; Yucesoy, Berran
• Description:
  Ortho-Phthalaldehyde (OPA) is increasingly being substituted for glutaraldehyde as a high-level disinfectant for sensitive medical devices. However, toxicological data on OPA safety is lacking. Safety concerns for glutaraldehyde include acute nasal toxicity and sensory irritation as well as sensitization leading to occupational rhinitis and asthma. Since OPA is a dialdehyde like glutaraldehyde and functions as a disinfectant due to its high reactivity for biological macromolecules, it is reasonable to expect similar respiratory hazards. Several case reports have been published supporting this hypothesis showing development of respiratory hypersensitivity reactions in healthcare workers and patients exposed to OPA. The purpose of this study was to determine if OPA is a respiratory sensitizer using a murine model. Mice were exposed via inhalation to OPA vapor 4 hrs/day for 3 days; rested for 11 days; challenged with OPA vapor 4 hrs/day for 3 days and then sacrificed 24 hrs after the final exposure. Lungs, nasal mucosa, head-draining lymph nodes (LN) and serum were collected and processed for cytokine gene expression and flow cytometry. OPA-specific antibodies were detected in the serum of exposed mice. OPA inhalation induced a dose dependent increase in LN IL-4 expression and B-cell proliferation. Importantly, there was a concomitant increase in IgE+ B-cells. Strong Th2 cytokine expression in the nasal mucosa increased with OPA dose whereas the inverse was observed for IFN(y) expression, a cytokine expression pattern commonly observed in response to respiratory allergens. Th2 cytokine expression was also increased in the lung although to a lesser extent. These data demonstrate that OPA inhalation induces a predominant Th2 cytokine response in the respiratory tract and draining LN. Importantly, OPA inhalation induced isotype switching to IgE in the draining LN supporting the development of an allergic immune response. Overall, this study suggests that inhalation of OPA vapor in mice can induce respiratory allergy. [Description provided by NIOSH]
• Subjects:
  Chemistry Cytotoxins Hazardous Substances Health Care Facilities Workforce And Services Health Personnel Hypersensitivity Irritants Laboratories Lung Lung Diseases Microbiology Occupational Health Respiratory Hypersensitivity Respiratory System Respiratory Tract Diseases Safety Toxicology

  More +
• Keywords:
  Allergic-reactions Biological-effects Cell-biology Cellular-reactions Chemical-cleaning Chemical-hypersensitivity Chemical-reactions Cytotoxic-effects Dose-response Exposure-levels Health-care-personnel Inhalation-studies Laboratory-animals Laboratory-testing Lung-cells Lung-disorders Lung-irritants Medical-facilities Microscopic-analysis Physiological-effects Quantitative-analysis Respiratory-hypersensitivity Respiratory-irritants Respiratory-system-disorders Statistical-analysis Toxic-dose Toxic-effects Toxic-vapors

  More +
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  District of Columbia ; OSHA Region 3 ; West Virginia
• 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:
  20
• Volume:
  120
• NIOSHTIC Number:
  nn:20038440
• Citation:
  Toxicologist 2011 Mar; 120(Suppl 2):20
• CAS Registry Number:
  Phthalaldehyde (CAS RN 643-79-8)
• Federal Fiscal Year:
  2011
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 50th Annual Meeting and ToxExpo, March 6-10, 2011, Washington, DC
• Supplement:
  2
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:872b423f83a7934877d1ee96c6f21302198c76a03fe3b446987a102859557fc9f422e92c4c174febebd80b3967ee2de03afe8c40f63a32d3c5f327b7972d68b3
• Download URL:
  https://stacks.cdc.gov/view/cdc/192152/cdc_192152_DS1.pdf
• File Type:
  [PDF - 3.93 MB ]