title: Evaluation of in vitro assays for the assessment of the skin sensitization hazard of functional polysiloxanes and silanes.
abstract: The skin sensitization potential of chemicals has traditionally been evaluated in vivo according to OECD testing guidelines in guinea pigs or the mouse local lymph node assay. There has lately been a great emphasis on establishing in vitro test methods reflecting the key biological events in the adverse outcome pathway (AOP) for skin sensitization as published by the OECD. Against this background, a group of 8 polysiloxanes and silanes, seven of them aminofunctionalised, for which in vivo data were already available, has been tested in vitro in the direct peptide reactivity assay (DPRA), the KeratinoSens™ and the human cell line activation test (h-CLAT) and in the modified myeloid U937 skin sensitization test (mMUSST) as far as technically feasible. The main objective of the programme was to determine the utility of these systems for this heterogeneous group of silicone-based substances, recognizing that some substances are outside the assays applicability domains. The presented data provided some interesting mechanistical insights into the performance of these assays for functionalised siloxanes and silanes. The data also allow for a preliminary evaluation of proposed integrated testing strategies (ITS) to determine the skin sensitization potential of chemicals which were not considered in the training sets of the respective ITS.
authors.affiliation: ToxMinds BVBA, Product Safety & Regulatory Affairs, B-1200 Brussels, Belgium. Electronic address: thomas.petry@toxminds.com.
authors.forename: Thomas
authors.initials: T
authors.lastname: Petry
authors.affiliation: Wacker Chemie AG, Corporate Product Safety, D-84489 Burghausen, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Bosch
authors.affiliation: Bluestar Silicones, F-69191 Saint Fons Cedex, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Coste
authors.affiliation: Evonik Nutrition & Care, GmbH Goldschmidtstr.100, D-45127 Essen, Germany.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Eigler
authors.affiliation: Centre Européen des Silicones, CEFIC, B-1160 Brussels, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Germain
authors.affiliation: Dow Corning Corporation, Health and Environmental Sciences, 2200 West Salzburg Road, Auburn, MI 48611, United States.
authors.forename: Shawn
authors.initials: S
authors.lastname: Seidel
authors.affiliation: Dow Corning Corporation, Health and Environmental Sciences, 2200 West Salzburg Road, Auburn, MI 48611, United States.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Jean
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D001681:Biological Assay; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D017449:Dermatitis, Allergic Contact / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005240:Feasibility Studies; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D006168:Guinea Pigs; D006801:Humans; D007509:Irritants / Q000633:toxicity*; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D023441:Local Lymph Node Assay; D008808:Mice, Inbred CBA; D018570:Risk Assessment; D012821:Silanes / Q000633:toxicity*; D012833:Siloxanes / Q000633:toxicity*; D023422:Skin Irritancy Tests / Q000379:methods*; D020298:U937 Cells
chemical_list: D007509:Irritants; D012821:Silanes; D012833:Siloxanes
keywords: DPRA; GPMT; In vitro; KeratinoSens™; LLNA; Polysiloxanes; Sensitization; Silanes; h-CLAT; mMUSST