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

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Marc A. T. Teunis1, Sander W. Spiekstra2, Mieke Smits1, Els Adriaens3, Tobias Eltze4, Valentina Galbiati5, Cyrille Krul1,6, Robert Landsiedel4, Raymond Pieters1,7, Judith Reinders2, Erwin Roggen8, Emanuela Corsini5 and Susan Gibbs2,9
1 University of Applied Sciences, Utrecht, The Netherlands;
2 Dept. Dermatology, VU University Medical Centre, Amsterdam, The Netherlands;
3 Adriaens Consulting, Statistical and Scientific Consultancy, Aalter, Belgium;
4 BASF SE, Ludwigshafen, Germany;
5 Laboratory of Toxicology, DiSFeB, Università degli Studi di Milano, Italy;
6 TNO, Zeist, The Netherlands;
7 Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands;
8 3Rs Management and Consultancy, Lyngby, Denmark;
9 Dept. Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), The Netherlands

Summary


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 to 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.

 

Keywords: in vitro, epidermal equivalent, sensitizer potency, NOEL, human DSA05



ALTEX 31(3), 251–268

DOI: http://dx.doi.org/10.14573/altex.1308021


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