Evaluation of Human Irritants and Weak to Moderate Sensitizers Using a Modified LLNA and an Irritancy/Phenotyping Assay

Details

• Personal Author:
  Hayes BB ; Howell MD ; Manetz TS ; Meade BJ ; Valosen JM ; Woolhiser MR
• Description:
  One reported weakness of the murine Local Lymph Node Assay (LLNA) is its inability to differentiate weak sensitizers and strong irritants. In these studies, we evaluated a panel of irritants and weak to moderate sensitizers in a modified LLNA and an irritancy/phenotypic analysis assay. Compounds initially tested included p-xylenol, thiomerosal, formaldehyde, benzocaine, menthol, and phenol. The LLNA protocol was modified to include pre and post ear measurements as an indication of irritation, The irritancy/phenotypic analysis method also used ear swelling as an indication of irritancy but evaluated sensitization by an elevation of the %B220+ and/or %IgE+B220+ (1gB-mediated) draining lymph node cell populations. In both assays, female BALB/c mice were topically exposed on the ear pinnae for 4 consecutive days. Ear measurements were taken prior to exposure on day 1 and 24 hr after final exposure on day 5. For the LLNA, [lH]-thymidine incorporation was measured on day 5 and for phenotypic analysis cell populations were examined on day 10. Consistent with the human literature, thiomerosal and formaldehyde were identified as irritants and sensitizers in both the modified LLNA and the irritancy/phenotypic assay. Additionally, the IgE+B220+ lymph node cell population was elevated in animals exposed to formaldehyde in agreement with reports of human contact urticaria following exposure to this compound. Phenol, a strong human irritant with a low sensitization index, was positive for irritation and sensitization in these assays. Benzocaine gave a false negative response for sensitization in both assays when tested at a 50% concentration in acetone. Although reported to be human irritants, menthol (50%), and p-xylenol (10%) were negative for both irritation and sensitization at the highest concentrations tested. [Description provided by NIOSH]
• Subjects:
  Animals Cells, Cultured Chemistry Chemistry, Analytic Ear Environmental Monitoring Hazardous Substances Hypersensitivity Irritants Laboratories Occupational Health Safety Sense Organs Toxicology

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• Keywords:
  Analytical-chemistry Analytical-methods Animal-studies Cell-cultures Cell-function Cellular-function Chemical-analysis Dose-response Ears Exposure-assessment Laboratory-animals Lymph-nodes Lymphatic-system Sensitivity-testing Sensitization Statistical-analysis Toxic-materials Toxins

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Louisiana ; OSHA Region 3 ; OSHA Region 6 ; Virginia ; 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:
  48
• NIOSHTIC Number:
  nn:20028032
• Citation:
  Toxicologist 1999 Mar; 48(1-S):313
• CAS Registry Number:
  Formaldehyde (CAS RN 50-00-0) ; Phenol (CAS RN 108-95-2)
• Federal Fiscal Year:
  1999
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 38th Annual Meeting, March 14-18, 1999, New Orleans, Louisiana
• Supplement:
  1-S
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:c5affadb091f46f8cc5a6aa5f4e00be3e8cb37b24b08d20e1a8a82a62734987533333cf0cd85abd7dad110d31e7d97b2c8548dd4a67a5f7cdde897d48321eddb
• Download URL:
  https://stacks.cdc.gov/view/cdc/189740/cdc_189740_DS1.pdf
• File Type:
  [PDF - 705.45 KB ]