TY - CHAP
T1 - Identification of contact allergens by in vitro cell culture-based methods
AU - Gibbs, Susan
AU - Martin, Stefan F.
AU - Corsini, Emanuela
AU - Thierse, Hermann Josef
PY - 2019/1/1
Y1 - 2019/1/1
N2 - If an in vitro model is to replace an animal model, it should perform to at least the same degree of accuracy as current animal models. Most importantly it should correlate to the human experience. Currently it is thought that no single assay will meet these requirements and that a battery of assays that mimic sensitization in vitro should be developed. It is thought that such a battery of human cell-based assays will mimic the human situation more than animal cell-based assays. Assays reflecting epidermal penetration and activation, dendritic cell maturation and migration, and T cell priming assays are being developed. The irritant property of a sensitizer may be related to sensitizer potency and may enable sensitizer potency to be determined with the aid of an epidermal equivalent assay. A proteomic approach to investigate the effect of chemical sensitizers on keratinocyte metabolism may identify novel biomarkers. Genomic and proteomic studies are identifying dendritic cell signatures which identify sensitizers from non-sensitizers. In vitro T cell priming assays can be used to distinguish sensitizers from non-sensitizers. The nature of these assays, however, makes it currently unlikely that they will be suitable for high-throughput screening. Progress toward validation is slow but steadily moving forward. A number of assays are being identified which may be suitable for pre-validation studies and then validation studies.
AB - If an in vitro model is to replace an animal model, it should perform to at least the same degree of accuracy as current animal models. Most importantly it should correlate to the human experience. Currently it is thought that no single assay will meet these requirements and that a battery of assays that mimic sensitization in vitro should be developed. It is thought that such a battery of human cell-based assays will mimic the human situation more than animal cell-based assays. Assays reflecting epidermal penetration and activation, dendritic cell maturation and migration, and T cell priming assays are being developed. The irritant property of a sensitizer may be related to sensitizer potency and may enable sensitizer potency to be determined with the aid of an epidermal equivalent assay. A proteomic approach to investigate the effect of chemical sensitizers on keratinocyte metabolism may identify novel biomarkers. Genomic and proteomic studies are identifying dendritic cell signatures which identify sensitizers from non-sensitizers. In vitro T cell priming assays can be used to distinguish sensitizers from non-sensitizers. The nature of these assays, however, makes it currently unlikely that they will be suitable for high-throughput screening. Progress toward validation is slow but steadily moving forward. A number of assays are being identified which may be suitable for pre-validation studies and then validation studies.
KW - AOP
KW - Cytokines
KW - DC maturation
KW - DC migration
KW - Dendritic Cell-Based Assays
KW - Epidermal equivalent (EE) potency assay
KW - Epidermal penetration
KW - GARD
KW - Genomics approach
KW - h-CLAT
KW - Human histiocytic lymphoma cell line U937
KW - Human monocytic leukaemia cell line THP1
KW - Human T cell priming assay (hTCPA)
KW - IL-18 biomarker assay
KW - In vitro skin sensitisation
KW - Keratinocytes
KW - MUTZ-3
KW - Nrf2-Keap1-Antioxidant Response Element (ARE)
KW - Proteomics approach
KW - U-SENS
UR - http://www.scopus.com/inward/record.url?scp=85088724767&partnerID=8YFLogxK
U2 - 10.1007/978-3-319-68617-2_106
DO - 10.1007/978-3-319-68617-2_106
M3 - Chapter
AN - SCOPUS:85088724767
SN - 9783319686158
SP - 1589
EP - 1607
BT - Kanerva's Occupational Dermatology
PB - Springer International Publishing AG
ER -