Experience with local lymph node assay performance standards using standard radioactivity and nonradioactive cell...

Area of Science:

• Toxicology
• Dermatology
• Immunotoxicology

Background:

• The local lymph node assay (LLNA) is the gold standard for identifying skin sensitizers.
• Nonradioactive alternatives to LLNA require validation against established performance standards (PS).

Purpose of the Study:

• To evaluate a lymph node cell count (LNCC) variant of the LLNA against harmonized minimum performance standards (PS).
• To assess the concordance between radioactive LLNA and nonradioactive LNCC measurements for skin sensitizers.

Main Methods:

• The LNCC assay was performed in parallel with the standard radioactive LLNA.
• Twenty-two performance standards (PS) chemicals were tested to determine threshold concentrations (EC3).
• Results from both methods were compared against established PS criteria.

Main Results:

• The LNCC assay demonstrated high agreement with the radioactive LLNA, with 21 out of 22 chemicals yielding concordant results.
• Minor discrepancies were observed for 2-mercaptobenzothiazole, methylmethacrylate, and nickel chloride.
• The LNCC method showed good accordance with radioactive measurements for most PS chemicals.

Conclusions:

• The lymph node cell count (LNCC) assay is a reliable nonradioactive alternative to the standard LLNA for skin sensitization testing.
• Validation against PS indicates LNCC can meet regulatory acceptance criteria.
• Careful analysis is needed when comparing results with published PS data.