title: Perspectives on Non-Animal Alternatives for Assessing Sensitization Potential in Allergic Contact Dermatitis.
abstract: Skin sensitization remains a major environmental and occupational health hazard. Animal models have been used as the gold standard method of choice for estimating chemical sensitization potential. However, a growing international drive and consensus for minimizing animal usage have prompted the development ofin vitromethods to assess chemical sensitivity. In this paper, we examine existing approaches includingin silicomodels, cell and tissue based assays for distinguishing between sensitizers and irritants. Thein silicoapproaches that have been discussed include Quantitative Structure Activity Relationships (QSAR) and QSAR based expert models that correlate chemical molecular structure with biological activity and mechanism based read-across models that incorporate compound electrophilicity. The cell and tissue based assays rely on an assortment of mono and co-culture cell systems in conjunction with 3D skin models. Given the complexity of allergen induced immune responses, and the limited ability of existing systems to capture the entire gamut of cellular and molecular events associated with these responses, we also introduce a microfabricated platform that can capture all the key steps involved in allergic contact sensitivity. Finally, we describe the development of an integrated testing strategy comprised of two or three tier systems for evaluating sensitization potential of chemicals.
authors.affiliation: Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, 231, Piscataway, NJ 08854, USA.
authors.forename: Nripen S
authors.initials: NS
authors.lastname: Sharma
authors.affiliation: Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, 231, Piscataway, NJ 08854, USA.
authors.forename: Rohit
authors.initials: R
authors.lastname: Jindal
authors.affiliation: Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, 231, Piscataway, NJ 08854, USA.
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Mitra
authors.affiliation: Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, 231, Piscataway, NJ 08854, USA.
authors.forename: Serom
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, 231, Piscataway, NJ 08854, USA.
authors.forename: Lulu
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, 231, Piscataway, NJ 08854, USA.
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Maguire
authors.affiliation: Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, 231, Piscataway, NJ 08854, USA.
authors.forename: Rene
authors.initials: R
authors.lastname: Schloss
authors.affiliation: Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, 231, Piscataway, NJ 08854, USA ; Center for Engineering in Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Yarmush
keywords: 2D cell based models; 3D skin tissue models; Immunobiology; In silico approaches; Integrated Testing Strategies; Microfabrication; Microfluidics; QSAR; Skin sensitization
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