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

ABSTRACT: Meaningful and accurate reference data are crucial for the validation of New Approach Methodologies (NAMs) in toxicology. For skin sensitization, multiple reference datasets are available including human patch test data, guinea pig data and data from the mouse local lymph node assay (LLNA). When assessed against the LLNA, a reduced sensitivity has been reported for in vitro and in chemico assays for lipophilic chemicals with a LogP ≥3.5, resulting in reliability restrictions within the h-CLAT OECD test guideline. Here we address the question of whether LLNA data are an appropriate reference for chemicals in this physicochemical range. Analysis of LLNA vs human reference data indicates that the false-discovery rate of the LLNA is significantly higher for chemicals with LogP ≥3.5. We present

SUBMITTER: Natsch A 

PROVIDER: S-EPMC9941753 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature