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Local lymph node assay (LLNA): Comparison of different protocols by testing skin-sensitizing epoxy resin system components
Affiliation:1. BASF SE, Experimental Toxicology and Ecology, 67056 Ludwigshafen, Germany;2. Institute for Occupational Safety and Health of the German Social Accident Insurance (BGIA), 53757 Sankt Augustin, Germany;3. Bayer HealthCare AG, Toxicology, Aprather Weg, 42096 Wuppertal, Germany;1. BASF SE, Experimental Toxicology and Ecology, 67056 Ludwigshafen, Germany;2. TNO, P.O. Box 360, 3700 AJ Zeist, The Netherlands;1. TNO, P.O. Box 360, 3700 AJ Zeist, The Netherlands;2. BASF SE, Experimental Toxicology and Ecology, 67056 Ludwigshafen, Germany;3. TNO, P.O. Box 6235, 5600 HE Eindhoven, The Netherlands;1. Department of Pharmacy, National University of Singapore, Lower Kent Ridge Road, 18 Science Drive 2, 117543, Singapore;2. Skin Research Institute of Singapore, 8A Biomedical Grove, #06-06, Immunos, 138648, Singapore;3. Le Studium Loire Valley Institute of Advanced Studies, 1 rue Dupanloup, 45000 Orléans and EA 6295 NanoMédicaments et NanoSondes, Faculté de Pharmacie, Université de Tours, 31 Avenue Monge, 37200 Tours, France;4. Department of Chemistry, National University of Singapore, Lower Kent Ridge Road, 18 Science Drive 2, 117543, Singapore;5. Department of Dermatology, Division of Dermato-Allergy, University of Minnesota, 420 Delaware St SE, Minneapolis, MN, 55455, United States;6. Department of Drug Discovery, College of Pharmacy, Medical University of South Carolina, 280 Calhoun St, Charleston, SC, 29425, United States;1. Department of Mechanical Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea;2. Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA;1. Department of Mechanical Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea;2. Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA;1. Instem, 1393 Dublin Rd, Columbus, OH 43215, USA;2. Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA;3. Alpha-PreTox, via G.Pascoli 1, 00184 Roma, Italy;4. Merck Healthcare KGaA, Frankfurter Str. 250, U009/101, Germany;5. R3Fellows LLC, Durham, NC, USA;6. School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK;7. Idorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, 4123 Allschwill, Switzerland;8. BASF SE, APD/ET, Li 444, Speyerer St 2, 67117 Limburgerhof, Germany;9. FStox Consulting LTD, 2 Brooks Road Raunds, Wellingborough NN9 6NS, UK;10. Laboratory of Environmental Chemistry and Toxicology, Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy;11. Chemical Food Safety Group, Nestlé Research, Lausanne, Switzerland;12. RTice Consulting, Hillsborough, NC 27278, USA;13. Transendix LLC, 1407 Moores Manor, Indianapolis, IN 46229, USA
Abstract:Thirteen epoxy resin system components were tested in the LLNA with regard to their sensitizing potency. Lymph node stimulation was quantified not only by measuring the incorporation of [3H]-thymidine into the ear lymph nodes but also the counts of cells recovered from these organs. Equivalent figures were obtained with both endpoints used for the evaluation of lymph node cell proliferation if the reference stimulation indices were adjusted. When dissolved in acetone, all test substances showed skin-sensitizing potential, mainly on the boundary between “strong” and “moderate” according to common potency evaluation schemes. Replacing acetone with acetone/olive oil (4:1) as a vehicle for four selected test items, resulted in considerably lower estimated concentrations for sensitization induction. The challenges in comparing the results obtained by different LLNA variations are discussed.
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