PMID- 25934255
OWN - NLM
STAT- MEDLINE
DCOM- 20160524
LR  - 20150803
IS  - 1096-0295 (Electronic)
IS  - 0273-2300 (Linking)
VI  - 72
IP  - 3
DP  - 2015 Aug
TI  - Extension of the Dermal Sensitisation Threshold (DST) approach to incorporate 
      chemicals classified as reactive.
PG  - 694-701
LID - S0273-2300(15)00097-5 [pii]
LID - 10.1016/j.yrtph.2015.04.020 [doi]
AB  - The evaluation of chemicals for their skin sensitising potential is an essential 
      step in ensuring the safety of ingredients in consumer products. Similar to the 
      Threshold of Toxicological Concern, the Dermal Sensitisation Threshold (DST) has 
      been demonstrated to provide effective risk assessments for skin sensitisation in 
      cases where human exposure is low. The DST was originally developed based on a 
      Local Lymph Node Assay (LLNA) dataset and applied to chemicals that were not 
      considered to be directly reactive to skin proteins, and unlikely to initiate the 
      first mechanistic steps leading to the induction of sensitisation. Here we have 
      extended the DST concept to protein reactive chemicals. A probabilistic 
      assessment of the original DST dataset was conducted and a threshold of 64 
      mug/cm(2) was derived. In our accompanying publication, a set of structural 
      chemistry based rules was developed to proactively identify highly reactive and 
      potentially highly potent materials which should be excluded from the DST 
      approach. The DST and rule set were benchmarked against a test set of chemicals 
      with LLNA/human data. It is concluded that by combining the reactive DST with 
      knowledge of chemistry a threshold can be established below which there is no 
      appreciable risk of sensitisation for protein-reactive chemicals.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Safford, Robert J
AU  - Safford RJ
AD  - B-Safe Toxicology Consulting, 31 Hayway, Rushden, Northants NN10 6AG, United 
      Kingdom. Electronic address: bob.safford@bstoxconsult.co.uk.
FAU - Api, Anne Marie
AU  - Api AM
AD  - Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff 
      Lake, NJ 07677, United States. Electronic address: amapi@rifm.org.
FAU - Roberts, David W
AU  - Roberts DW
AD  - School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, 
      Byrom Street, Liverpool L3 3AF, United Kingdom. Electronic address: 
      d.w.roberts@ljmu.ac.uk.
FAU - Lalko, Jon F
AU  - Lalko JF
AD  - Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff 
      Lake, NJ 07677, United States. Electronic address: jlalko@rifm.org.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150429
PL  - Netherlands
TA  - Regul Toxicol Pharmacol
JT  - Regulatory toxicology and pharmacology : RTP
JID - 8214983
RN  - 0 (Allergens)
RN  - 0 (Proteins)
SB  - IM
MH  - Allergens/*toxicity
MH  - Animals
MH  - Biological Assay
MH  - Databases, Factual
MH  - Dermatitis, Allergic Contact/*ethnology
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Lymph Nodes/immunology
MH  - No-Observed-Adverse-Effect Level
MH  - Proteins/metabolism
MH  - Risk Assessment/*methods
OTO - NOTNLM
OT  - Dermal Sensitisation Threshold (DST)
OT  - Local Lymph Node Assay (LLNA)
OT  - Non-animal methods
OT  - Sensitisation risk assessment
OT  - Skin sensitisation
EDAT- 2015/05/03 06:00
MHDA- 2016/05/25 06:00
CRDT- 2015/05/03 06:00
PHST- 2014/11/28 00:00 [received]
PHST- 2015/04/16 00:00 [revised]
PHST- 2015/04/17 00:00 [accepted]
PHST- 2015/05/03 06:00 [entrez]
PHST- 2015/05/03 06:00 [pubmed]
PHST- 2016/05/25 06:00 [medline]
AID - S0273-2300(15)00097-5 [pii]
AID - 10.1016/j.yrtph.2015.04.020 [doi]
PST - ppublish
SO  - Regul Toxicol Pharmacol. 2015 Aug;72(3):694-701. doi: 
      10.1016/j.yrtph.2015.04.020. Epub 2015 Apr 29.