title: 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-EC50) or the 2-fold increase in IL-1α (IL-1α2x). Four laboratories received 13 coded sensitizers. Reproducible results were obtained in each laboratory. A binary prediction model, EC50≥7 mg/ml=weak to moderate sensitizer and EC50<7 mg/ml=strong to extreme sensitizer had an accuracy of 77%. A superior EE (EC50 and IL-1α2x) correlation was observed with human in vivo DSA05 data compared to LLNA-EC3 data. Human in vivo NOEL and LLNA-EC3 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.
authors.affiliation: University of Applied Sciences, Utrecht, The Netherlands.
authors.forename: Marc A T
authors.initials: MA
authors.lastname: Teunis
authors.forename: Sander W
authors.initials: SW
authors.lastname: Spiekstra
authors.forename: Mieke
authors.initials: M
authors.lastname: Smits
authors.forename: Els
authors.initials: E
authors.lastname: Adriaens
authors.forename: Tobias
authors.initials: T
authors.lastname: Eltze
authors.forename: Valentina
authors.initials: V
authors.lastname: Galbiati
authors.forename: Cyrille
authors.initials: C
authors.lastname: Krul
authors.forename: Robert
authors.initials: R
authors.lastname: Landsiedel
authors.forename: Raymond
authors.initials: R
authors.lastname: Pieters
authors.forename: Judith
authors.initials: J
authors.lastname: Reinders
authors.forename: Erwin
authors.initials: E
authors.lastname: Roggen
authors.forename: Emanuela
authors.initials: E
authors.lastname: Corsini
authors.forename: Susan
authors.initials: S
authors.lastname: Gibbs
mesh_terms: D000485:Allergens / Q000009:adverse effects* / Q000737:chemistry; D000826:Animal Testing Alternatives; D000818:Animals; D002478:Cells, Cultured; D017449:Dermatitis, Allergic Contact / Q000209:etiology*; D004817:Epidermis / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D020382:Interleukin-18 / Q000276:immunology / Q000378:metabolism; D023441:Local Lymph Node Assay; D051379:Mice; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D018675:Toxicity Tests / Q000379:methods
chemical_list: D000485:Allergens; D020382:Interleukin-18