Reduced specificity for the local lymph node assay for lipophilic chemicals: Implications for the validation of new approach methods for skin sensitization

• DOI: 10.1016/j.yrtph.2023.105333
• Publication Date: 2023-01-03T16:27:55Z
• Authors: Andreas Natsch; Nicole Kleinstreuer; David Asturiol
• Keywords: In vitro toxicology; Chemical compound

Meaningful and accurate reference data are crucial for the validation of New Approach Methodologies (NAMs) in toxicology. For skin sensitization, multiple datasets available including human patch test data, guinea pig from mouse local lymph node assay (LLNA). When assessed against LLNA, a reduced sensitivity has been reported vitro chemico assays lipophilic chemicals with LogP ≥3.5, resulting reliability restrictions within h-CLAT OECD guideline. Here we address question whether LLNA an appropriate this physicochemical range. Analysis vs indicates that false-discovery rate is significantly higher ≥3.5. We present mechanistic hypothesis whereby irritation caused by testing at high doses leads to unspecific cell proliferation. The accompanying analysis negative calls assays, resorting not necessarily better option. These results indicate NAMs particular range should be based on more holistic evaluation solely upon data.