PMID- 31100378
OWN - NLM
STAT- MEDLINE
DCOM- 20200210
LR  - 20200210
IS  - 1879-3177 (Electronic)
IS  - 0887-2333 (Linking)
VI  - 60
DP  - 2019 Oct
TI  - Assessment of a defined approach based on a stacking prediction model to identify 
      skin sensitization hazard.
PG  - 134-143
LID - S0887-2333(18)30758-6 [pii]
LID - 10.1016/j.tiv.2019.05.008 [doi]
AB  - Skin sensitization is an important toxicological endpoint in the safety 
      assessment of chemicals and cosmetic ingredients. Driven by ethical 
      considerations and European Union (EU) legislation, its assessment has progressed 
      from the reliance on traditional animal models to the use of non-animal test 
      methods. It is generally accepted that the assessment of skin sensitization 
      requires the integration of various non-animal test methods in defined approaches 
      (DAs), to cover the mechanistic key events of the adverse outcomes pathway (AOP) 
      (OECD, 2014). Several case studies for DAs predicting skin sensitization hazard 
      or potency have been submitted to the OECD, including a stacking meta-model 
      developed by L'Oreal Research & Innovation (OECD, 2017b; Del Bufalo et al., 2018; 
      Nocairi et al., 2016). The present study evaluated the predictive performance of 
      the defined approach integrating a stacking meta-model incorporating in silico, 
      in chemico and in vitro assays, using the Cosmetics Europe (CE) skin 
      sensitization database. Based on the optimized prediction cut-offs, the defined 
      approach provided a hazard prediction for 97 chemicals with a sensitivity of 91%, 
      a specificity of 76% and accuracy of 86% (kappa of 0.67) against human skin 
      sensitization hazard data and a sensitivity of 85%, specificity of 91% and 
      accuracy of 87% (kappa of 0.67) against Local Lymph Node Assay (LLNA) hazard 
      data. A comparison of the in vivo LLNA with human hazard data for the same 97 
      chemicals showed a sensitivity of 92%, specificity of 51% and accuracy of 78% 
      (kappa of 0.48). Thus, the defined approach showed a higher degree of 
      concordance, as compared to the LLNA for predicting human skin sensitization 
      hazard. Moreover, a comparison with the six DAs selected for evaluation of their 
      predictivity in the study by Kleinstreuer et al. (2018) showed a similar high 
      accuracy of 86% for 97 overlapping chemicals. The next step will be an 
      independent evaluation of the DA for its integration in the performances based 
      test guidelines (PBTG) for skin sensitization.
CI  - Copyright (c) 2019 Elsevier Ltd. All rights reserved.
FAU - Tourneix, Fleur
AU  - Tourneix F
AD  - L'Oreal Research & Innovation, Aulnay-sous-Bois, France. Electronic address: 
      fleur.tourneix@rd.loreal.com.
FAU - Alepee, Nathalie
AU  - Alepee N
AD  - L'Oreal Research & Innovation, Aulnay-sous-Bois, France.
FAU - Detroyer, Ann
AU  - Detroyer A
AD  - L'Oreal Research & Innovation, Aulnay-sous-Bois, France.
FAU - Eilstein, Joan
AU  - Eilstein J
AD  - L'Oreal Research & Innovation, Aulnay-sous-Bois, France.
FAU - Martinozzi Teissier, Silvia
AU  - Martinozzi Teissier S
AD  - L'Oreal Research & Innovation, Aulnay-sous-Bois, France.
FAU - Nardelli, Laurent
AU  - Nardelli L
AD  - L'Oreal Research & Innovation, Aulnay-sous-Bois, France.
FAU - Nocairi, Hicham
AU  - Nocairi H
AD  - L'Oreal Research & Innovation, Aulnay-sous-Bois, France.
FAU - Pauloin, Thierry
AU  - Pauloin T
AD  - L'Oreal Research & Innovation, Aulnay-sous-Bois, France.
FAU - Piroird, Cecile
AU  - Piroird C
AD  - L'Oreal Research & Innovation, Aulnay-sous-Bois, France.
FAU - Del Bufalo, Aurelia
AU  - Del Bufalo A
AD  - L'Oreal Research & Innovation, Aulnay-sous-Bois, France.
LA  - eng
PT  - Journal Article
DEP - 20190514
PL  - England
TA  - Toxicol In Vitro
JT  - Toxicology in vitro : an international journal published in association with 
      BIBRA
JID - 8712158
RN  - 0 (Haptens)
SB  - IM
MH  - Animal Testing Alternatives
MH  - Computer Simulation
MH  - Databases, Factual
MH  - Dermatitis, Allergic Contact
MH  - Haptens/*toxicity
MH  - Humans
MH  - *Models, Biological
OTO - NOTNLM
OT  - Defined approach
OT  - Hazard identification
OT  - In silico
OT  - In vitro
OT  - Risk assessment
OT  - Skin sensitization
EDAT- 2019/05/18 06:00
MHDA- 2020/02/11 06:00
CRDT- 2019/05/18 06:00
PHST- 2018/11/22 00:00 [received]
PHST- 2019/05/10 00:00 [revised]
PHST- 2019/05/13 00:00 [accepted]
PHST- 2019/05/18 06:00 [pubmed]
PHST- 2020/02/11 06:00 [medline]
PHST- 2019/05/18 06:00 [entrez]
AID - S0887-2333(18)30758-6 [pii]
AID - 10.1016/j.tiv.2019.05.008 [doi]
PST - ppublish
SO  - Toxicol In Vitro. 2019 Oct;60:134-143. doi: 10.1016/j.tiv.2019.05.008. Epub 2019 
      May 14.