title: Assessing skin sensitization hazard in mice and men using non-animal test methods.
abstract: Sensitization, the prerequisite event in the development of allergic contact dermatitis, is a key parameter in both hazard and risk assessments. The pathways involved have recently been formally described in the OECD adverse outcome pathway (AOP) for skin sensitization. One single non-animal test method will not be sufficient to fully address this AOP and in many cases the use of a battery of tests will be necessary. A number of methods are now fully developed and validated. In order to facilitate acceptance of these methods by both the regulatory and scientific communities, results of the single test methods (DPRA, KeratinoSens, LuSens, h-CLAT, (m)MUSST) as well for a the simple '2 out of 3' ITS for 213 substances have been compiled and qualitatively compared to both animal and human data. The dataset was also used to define different mechanistic domains by probable protein-binding mechanisms. In general, the non-animal test methods exhibited good predictivities when compared to local lymph node assay (LLNA) data and even better predictivities when compared to human data. The '2 out of 3' prediction model achieved accuracies of 90% or 79% when compared to human or LLNA data, respectively and thereby even slightly exceeded that of the LLNA.
authors.affiliation: BASF SE, Experimental Toxicology and Ecology, Ludwigshafen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Urbisch
authors.affiliation: BASF Personal Care and Nutrition GmbH, Düsseldorf, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Mehling
authors.affiliation: BASF SE, Experimental Toxicology and Ecology, Ludwigshafen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Guth
authors.affiliation: BASF SE, Experimental Toxicology and Ecology, Ludwigshafen, Germany.
authors.forename: Tzutzuy
authors.initials: T
authors.lastname: Ramirez
authors.affiliation: BASF SE, Experimental Toxicology and Ecology, Ludwigshafen, Germany.
authors.forename: Naveed
authors.initials: N
authors.lastname: Honarvar
authors.affiliation: BASF SE, Experimental Toxicology and Ecology, Ludwigshafen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Kolle
authors.affiliation: BASF SE, Experimental Toxicology and Ecology, Ludwigshafen, Germany. Electronic address: robert.landsiedel@basf.com.
authors.forename: Robert
authors.initials: R
authors.lastname: Landsiedel
authors.affiliation: Procter & Gamble NV, 100 Temselaan, 1853 Strombeek-Bever, Belgium.
authors.forename: Joanna
authors.initials: J
authors.lastname: Jaworska
authors.affiliation: Procter & Gamble Technology (Beijing) Co., Ltd., China.
authors.forename: Petra S
authors.initials: PS
authors.lastname: Kern
authors.affiliation: Procter & Gamble Company, Cincinnati, OH, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Gerberick
authors.affiliation: Givaudan Schweiz AG, Ueberlandstraße 138, CH-8600 Dübendorf, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Natsch
authors.affiliation: Givaudan Schweiz AG, Ueberlandstraße 138, CH-8600 Dübendorf, Switzerland.
authors.forename: Roger
authors.initials: R
authors.lastname: Emter
authors.affiliation: Shiseido Research Center, Shiseido Co., Ltd., 2-2-1 Hayabuchi, Tsuzuki-ku, Yokohama-shi, Kanagawa 224-8558, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Ashikaga
authors.affiliation: Safety Science Research Laboratories, Kao Corporation, 2606 Akabane, Ichikai, Haga, Tochigi 321-349, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Miyazawa
authors.affiliation: Safety Science Research Laboratories, Kao Corporation, 2606 Akabane, Ichikai, Haga, Tochigi 321-349, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sakaguchi
mesh_terms: D000826:Animal Testing Alternatives / Q000379:methods*; D000818:Animals; D002460:Cell Line; D016208:Databases, Factual; D003879:Dermatologic Agents / Q000633:toxicity*; D006801:Humans; D051379:Mice; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D020298:U937 Cells
chemical_list: D003879:Dermatologic Agents
keywords: (modified) MUSST; Adverse outcome pathway (AOP); Allergic contact dermatitis (ACD); DPRA; Database; Integrated testing strategy (ITS); KeratinoSens™; LuSens; Skin sensitization; h-CLAT