PMID- 33124094
OWN - NLM
STAT- MEDLINE
DCOM- 20211221
LR  - 20211221
IS  - 1099-1263 (Electronic)
IS  - 0260-437X (Linking)
VI  - 41
IP  - 6
DP  - 2021 Jun
TI  - Characterization of dermal sensitization potential for industrial or agricultural 
      chemicals with EpiSensA.
PG  - 915-927
LID - 10.1002/jat.4076 [doi]
AB  - The regulatory community is transitioning to the use of nonanimal methods for 
      dermal sensitization assessments; however, some in vitro assays have limitations 
      in their domain of applicability depending on the properties of chemicals being 
      tested. This study explored the utility of epidermal sensitization assay 
      (EpiSensA) to evaluate the sensitization potential of complex and/or "difficult 
      to test" chemicals. Assay performance was evaluated by testing a set of 20 test 
      chemicals including 10 methacrylate esters, 5 silicone-based compounds, 3 crop 
      protection formulations, and 2 surfactant mixtures; each had prior in vivo data 
      plus some in silico and in vitro data. Using the weight of evidence (WoE) 
      assessments by REACH Lead Registrants, 14 of these chemicals were sensitizers 
      and, six were nonsensitizers based on in vivo studies (local lymph node assay 
      [LLNA] and/or guinea pig studies). The EpiSensA correctly predicted 16/20 
      materials with three test materials as false positive and one silane as false 
      negative. This silane, classified as weak sensitizer via LLNA, also gave a "false 
      negative" result in the KeratinoSens assay. Overall, consistent with prior 
      evaluations, the EpiSensA demonstrated an accuracy level of 80% relative to 
      available in vivo WoE assessments. In addition, potency classification based on 
      the concentration showing positive marker gene expression of EpiSensA was 
      performed. The EpiSensA correctly predicted the potency for all seven sensitizing 
      methacrylates classified as weak potency via LLNA (EC3 >/= 10%). In summary, 
      EpiSensA could identify dermal sensitization potential of these test substances 
      and mixtures, and continues to show promise as an in vitro alternative method for 
      dermal sensitization.
CI  - (c) 2020 John Wiley & Sons, Ltd.
FAU - Mizumachi, Hideyuki
AU  - Mizumachi H
AUID- ORCID: 0000-0001-8778-1951
AD  - R&D, Safety Science Research, Kao Corporation, Tochigi, Japan.
FAU - LeBaron, Matthew J
AU  - LeBaron MJ
AD  - Toxicology & Environmental Research & Consulting, Dow Chemical Company, Midland, 
      Michigan, USA.
FAU - Settivari, Raja S
AU  - Settivari RS
AD  - Corteva Agriscience, Haskell R&D Center, Newark, Delaware, USA.
FAU - Miyazawa, Masaaki
AU  - Miyazawa M
AD  - R&D, Safety Science Research, Kao Corporation, Tochigi, Japan.
FAU - Marty, Mary Sue
AU  - Marty MS
AD  - Toxicology & Environmental Research & Consulting, Dow Chemical Company, Midland, 
      Michigan, USA.
FAU - Sakaguchi, Hitoshi
AU  - Sakaguchi H
AD  - R&D, Safety Science Research, Kao Corporation, Tochigi, Japan.
LA  - eng
PT  - Journal Article
DEP - 20201030
PL  - England
TA  - J Appl Toxicol
JT  - Journal of applied toxicology : JAT
JID - 8109495
RN  - 0 (Agrochemicals)
RN  - 0 (Allergens)
RN  - 0 (Haptens)
SB  - IM
MH  - Agrochemicals/*toxicity
MH  - Allergens
MH  - Animal Testing Alternatives/methods
MH  - Animals
MH  - Biological Assay
MH  - Cell Line
MH  - Dermatitis, Allergic Contact
MH  - Epidermis
MH  - Guinea Pigs
MH  - Haptens
MH  - Humans
MH  - In Vitro Techniques
MH  - Local Lymph Node Assay
MH  - Skin
MH  - *Skin Tests
OTO - NOTNLM
OT  - DPRA
OT  - EpiSensA
OT  - KeratinoSens
OT  - h-CLAT
OT  - in vitro
OT  - skin sensitization
EDAT- 2020/10/31 06:00
MHDA- 2021/12/22 06:00
CRDT- 2020/10/30 06:00
PHST- 2020/09/02 00:00 [revised]
PHST- 2020/04/22 00:00 [received]
PHST- 2020/09/02 00:00 [accepted]
PHST- 2020/10/31 06:00 [pubmed]
PHST- 2021/12/22 06:00 [medline]
PHST- 2020/10/30 06:00 [entrez]
AID - 10.1002/jat.4076 [doi]
PST - ppublish
SO  - J Appl Toxicol. 2021 Jun;41(6):915-927. doi: 10.1002/jat.4076. Epub 2020 Oct 30.