PMID- 37846211
OWN - NLM
STAT- MEDLINE
DCOM- 20240214
LR  - 20240214
IS  - 1099-1263 (Electronic)
IS  - 0260-437X (Linking)
VI  - 44
IP  - 3
DP  - 2024 Mar
TI  - Reconstructed human epidermis-based testing strategy of skin sensitization 
      potential and potency classification using epidermal sensitization assay and in 
      silico data.
PG  - 415-427
LID - 10.1002/jat.4551 [doi]
AB  - The hazards and potency of skin sensitizers are traditionally determined using 
      animal tests such as the local lymph node assay (LLNA); however, significant 
      progress has been made in the development of non-animal test methods addressing 
      the first three mechanistic key events of adverse outcome pathway in skin 
      sensitization. We developed the epidermal sensitization assay (EpiSensA), which 
      is a reconstructed human epidermis-based assay, by measuring four genes related 
      to critical keratinocyte responses during skin sensitization. Four in vitro skin 
      sensitization test methods (EpiSensA, direct peptide reactivity assay [DPRA], 
      KeratinoSens, and human cell line activation test [h-CLAT]) were systematically 
      evaluated using 136 chemicals including lipophilic chemicals and pre/pro-haptens, 
      which may be related to assay-specific limitations. The constructed database 
      included existing and newly generated data. The EpiSensA showed a broader 
      applicability domain and predicted the hazards with 82.4% and 78.8% accuracy than 
      LLNA and human data. The EpiSensA could detect 76 out of 88 sensitizers at lower 
      concentrations than the LLNA, indicating that the EpiSensA has higher sensitivity 
      for the detection of minor sensitizing constituents. These results confirmed the 
      potential use of the EpiSensA in evaluating a mixture of unknown compositions 
      that can be evaluated by animal tests. To combine different information sources, 
      the reconstructed human epidermis-based testing strategy (RTS) was developed 
      based on weighted multiple information from the EpiSensA and TImes MEtabolism 
      Simulator platform for predicting Skin Sensitization (TIMES-SS; RTSv1) or 
      Organization for Economic Cooperation and Development (OECD) QSAR Toolbox 
      automated workflow (RTSv2). The predictivities of the hazards and Globally 
      Harmonized System (GHS) subcategories were equal to or better than the defined 
      approaches (2 out of 3, integrated testing strategy [ITS]v1, and ITSv2) adopted 
      as OECD Guideline 497.
CI  - (c) 2023 The Authors. Journal of Applied Toxicology published by John Wiley & Sons 
      Ltd.
FAU - Mizumachi, Hideyuki
AU  - Mizumachi H
AUID- ORCID: 0000-0001-8778-1951
AD  - Safety Science Research, Kao Corporation, Haga-gun, Japan.
FAU - Suzuki, Sho
AU  - Suzuki S
AD  - Safety Science Research, Kao Corporation, Haga-gun, Japan.
FAU - Sakuma, Megumi
AU  - Sakuma M
AD  - Safety and Analytical Research Laboratories, KOSE Corporation, Tokyo, Japan.
FAU - Natsui, Midori
AU  - Natsui M
AD  - Safety Science Research, Kao Corporation, Haga-gun, Japan.
FAU - Imai, Noriyasu
AU  - Imai N
AUID- ORCID: 0000-0003-1488-4292
AD  - Safety and Analytical Research Laboratories, KOSE Corporation, Tokyo, Japan.
FAU - Miyazawa, Masaaki
AU  - Miyazawa M
AD  - Safety Science Research, Kao Corporation, Haga-gun, Japan.
LA  - eng
PT  - Journal Article
DEP - 20231017
PL  - England
TA  - J Appl Toxicol
JT  - Journal of applied toxicology : JAT
JID - 8109495
SB  - IM
MH  - Animals
MH  - Humans
MH  - *Animal Testing Alternatives/methods
MH  - Skin
MH  - Epidermis
MH  - Keratinocytes/metabolism
MH  - Skin Tests
MH  - Local Lymph Node Assay
MH  - *Dermatitis, Allergic Contact/etiology/metabolism
OTO - NOTNLM
OT  - alternative method
OT  - lipophilic chemicals
OT  - potency prediction
OT  - pre/pro-haptens
OT  - reconstructed human epidermis-based testing strategy
OT  - skin sensitization
EDAT- 2023/10/17 06:42
MHDA- 2024/02/12 15:42
CRDT- 2023/10/17 03:49
PHST- 2023/09/24 00:00 [revised]
PHST- 2023/07/31 00:00 [received]
PHST- 2023/09/24 00:00 [accepted]
PHST- 2024/02/12 15:42 [medline]
PHST- 2023/10/17 06:42 [pubmed]
PHST- 2023/10/17 03:49 [entrez]
AID - 10.1002/jat.4551 [doi]
PST - ppublish
SO  - J Appl Toxicol. 2024 Mar;44(3):415-427. doi: 10.1002/jat.4551. Epub 2023 Oct 17.