PMID- 27569201
OWN - NLM
STAT- MEDLINE
DCOM- 20170316
LR  - 20181202
IS  - 1096-0295 (Electronic)
IS  - 0273-2300 (Linking)
VI  - 82
DP  - 2016 Dec
TI  - Can currently available non-animal methods detect pre and pro-haptens relevant 
      for skin sensitization?
PG  - 147-155
LID - S0273-2300(16)30228-8 [pii]
LID - 10.1016/j.yrtph.2016.08.007 [doi]
AB  - Predictive testing to characterize substances for their skin sensitization 
      potential has historically been based on animal tests such as the Local Lymph 
      Node Assay (LLNA). In recent years, regulations in the cosmetics and chemicals 
      sectors have provided strong impetus to develop non-animal alternatives. Three 
      test methods have undergone OECD validation: the direct peptide reactivity assay 
      (DPRA), the KeratinoSens and the human Cell Line Activation Test (h-CLAT). 
      Whilst these methods perform relatively well in predicting LLNA results, a 
      concern raised is their ability to predict chemicals that need activation to be 
      sensitizing (pre- or pro-haptens). This current study reviewed an EURL ECVAM 
      dataset of 127 substances for which information was available in the LLNA and 
      three non-animal test methods. Twenty eight of the sensitizers needed to be 
      activated, with the majority being pre-haptens. These were correctly identified 
      by 1 or more of the test methods. Six substances were categorized exclusively as 
      pro-haptens, but were correctly identified by at least one of the cell-based 
      assays. The analysis here showed that skin metabolism was not likely to be a 
      major consideration for assessing sensitization potential and that sensitizers 
      requiring activation could be identified correctly using one or more of the 
      current non-animal methods.
CI  - Published by Elsevier Inc.
FAU - Patlewicz, Grace
AU  - Patlewicz G
AD  - US Environmental Protection Agency, National Center for Computational Toxicology, 
      Research Triangle Park, NC, USA. Electronic address: patlewicz.grace@epa.gov.
FAU - Casati, Silvia
AU  - Casati S
AD  - European Commission, Joint Research Centre, Directorate F - Health, Consumers and 
      Reference Materials, Chemical Safety and Alternative Methods Unit, Ispra, VA, 
      Italy.
FAU - Basketter, David A
AU  - Basketter DA
AD  - DABMEB Consultancy Ltd, Sharnbrook, Bedfordshire, UK.
FAU - Asturiol, David
AU  - Asturiol D
AD  - European Commission, Joint Research Centre, Directorate F - Health, Consumers and 
      Reference Materials, Chemical Safety and Alternative Methods Unit, Ispra, VA, 
      Italy.
FAU - Roberts, David W
AU  - Roberts DW
AD  - Liverpool John Moores University, School of Pharmacy and Biomolecular Sciences, 
      Liverpool, UK.
FAU - Lepoittevin, Jean-Pierre
AU  - Lepoittevin JP
AD  - Institute of Chemistry, CNRS UMR 7177 and University of Strasbourg, Strasbourg, 
      France.
FAU - Worth, Andrew P
AU  - Worth AP
AD  - European Commission, Joint Research Centre, Directorate F - Health, Consumers and 
      Reference Materials, Chemical Safety and Alternative Methods Unit, Ispra, VA, 
      Italy.
FAU - Aschberger, Karin
AU  - Aschberger K
AD  - European Commission, Joint Research Centre, Directorate F - Health, Consumers and 
      Reference Materials, Chemical Safety and Alternative Methods Unit, Ispra, VA, 
      Italy.
LA  - eng
PT  - Congress
DEP - 20160826
PL  - Netherlands
TA  - Regul Toxicol Pharmacol
JT  - Regulatory toxicology and pharmacology : RTP
JID - 8214983
RN  - 0 (Haptens)
RN  - 0 (Irritants)
SB  - IM
MH  - Animal Testing Alternatives/*methods
MH  - Animals
MH  - Cell Line
MH  - Databases, Factual
MH  - Dermatitis, Allergic Contact/*etiology/immunology/pathology
MH  - Haptens/*toxicity
MH  - Humans
MH  - Irritants/*toxicity
MH  - Local Lymph Node Assay
MH  - Reproducibility of Results
MH  - Risk Assessment
MH  - Skin/*drug effects/immunology/pathology
MH  - Skin Irritancy Tests/*methods
MH  - Workflow
OTO - NOTNLM
OT  - Adverse Outcome Pathway
OT  - DPRA
OT  - KeratinoSens
OT  - Pre-hapten
OT  - Pro-hapten
OT  - Reaction mechanistic domain
OT  - Skin sensitization
OT  - h-CLAT
EDAT- 2016/08/30 06:00
MHDA- 2017/03/17 06:00
CRDT- 2016/08/30 06:00
PHST- 2016/08/10 00:00 [received]
PHST- 2016/08/18 00:00 [accepted]
PHST- 2016/08/30 06:00 [pubmed]
PHST- 2017/03/17 06:00 [medline]
PHST- 2016/08/30 06:00 [entrez]
AID - S0273-2300(16)30228-8 [pii]
AID - 10.1016/j.yrtph.2016.08.007 [doi]
PST - ppublish
SO  - Regul Toxicol Pharmacol. 2016 Dec;82:147-155. doi: 10.1016/j.yrtph.2016.08.007. 
      Epub 2016 Aug 26.