International ring trial of the epidermal equivalent sensitizer potency assay: Reproducibility and predictive capacity

Abstract

This study describes the international ring trial of the epidermal-equivalent (EE) sensitizer potency assay. This assay does not distinguish a sensitizer from a non-sensitizer, but may classify known skin sensitizers according to their potency. It assesses the chemical concentration resulting in 50% cytotoxicity (EE-EC 50) or the 2-fold increase in IL-1α (IL-1α 2x). Four laboratories received 13 coded sensitizers. Reproducible results were obtained in each laboratory. A binary prediction model, EC 50 ≥7 mg/ml = weak to moderate sensitizer and EC 50 <7 mg/ml = strong to extreme sensitizer had an accuracy of 77%. A superior EE (EC 50 and IL-1α 2x) correlation was observed to human in vivo DSA 05 data compared to LLNA-EC 3 data. Human in vivo NOEL and LLNA-EC 3 data correlated to a similar extent to in vitro EE data. Our results indicate that this easily transferable EE potency assay is suitable for testing chemical allergens of unknown potencies and may now be ready for further validation, providing complementary potency information to other assays already undergoing validation for assessing skin sensitization potential.