PMID- 32562760
OWN - NLM
STAT- MEDLINE
DCOM- 20210325
LR  - 20210325
IS  - 1096-0295 (Electronic)
IS  - 0273-2300 (Linking)
VI  - 115
DP  - 2020 Aug
TI  - Replacing the refinement for skin sensitization testing: Considerations to the 
      implementation of adverse outcome pathway (AOP)-based defined approaches (DA) in 
      OECD guidelines.
PG  - 104713
LID - S0273-2300(20)30139-2 [pii]
LID - 10.1016/j.yrtph.2020.104713 [doi]
AB  - While single non-animal methods have been adopted in OECD test guidelines, 
      combinations of methods (so called defined approaches, DA) are not. Hardly any 
      animal study can be replaced by a single non-animal method, rather DA are needed. 
      The OECD published the Adverse Outcome Pathway (AOP) on skin sensitization in 
      2012 and is currently discussing the implementation of DA into a guideline. 
      Obviously, it takes thorough considerations and evaluations to validate such DA. 
      Currently we see four preconditions for a proper and expedient implementation of 
      DA in a guideline: (i) The reference data should be selected to allow meaningful 
      evaluations and must not replicate the limitations of the murine local lymph node 
      assay (LLNA) (ii) Methods and prediction models should be validated before they 
      are used in an OECD-adopted DA, (iii) An OECD-adopted DA should follow the 
      respective AOP and (iv) acknowledge regulatory needs and successful toxicological 
      practice. These points still need to be considered in the current discussion at 
      the OECD. A guideline for skin sensitization DA is setting the scene for 
      regulatory acceptance of all new approaches (for any toxicological endpoint) in 
      the future. In this commentary, we are expounding these preconditions to allow a 
      scientifically valid and sustainable application of modern (no-animal) approaches 
      in regulatory toxicology.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Kolle, Susanne N
AU  - Kolle SN
AD  - BASF SE, Experimental Toxicology and Ecology, 67056, Ludwigshafen am Rhein, 
      Germany.
FAU - Landsiedel, Robert
AU  - Landsiedel R
AD  - BASF SE, Experimental Toxicology and Ecology, 67056, Ludwigshafen am Rhein, 
      Germany. Electronic address: robert.landsiedel@basf.com.
FAU - Natsch, Andreas
AU  - Natsch A
AD  - Givaudan Schweiz AG, Kemptpark 50, 8310, Kemptthal, Switzerland.
LA  - eng
PT  - Journal Article
DEP - 20200617
PL  - Netherlands
TA  - Regul Toxicol Pharmacol
JT  - Regulatory toxicology and pharmacology : RTP
JID - 8214983
SB  - IM
MH  - *Adverse Outcome Pathways
MH  - Animal Testing Alternatives
MH  - *Dermatitis, Allergic Contact
MH  - Guidelines as Topic
MH  - Humans
MH  - Organisation for Economic Co-Operation and Development
MH  - *Skin Irritancy Tests
OTO - NOTNLM
OT  - Adverse outcome pathway(AOP)
OT  - Defined approach (DA)
OT  - Integrated Approach for Testing and Assessment (IATA)
OT  - Non-animal methods
OT  - OECD test guideline
OT  - Skin sensitization
OT  - Validation
COIS- Declaration of competing interest The authors declare the following financial 
      interests/personal relationships which may be considered as potential competing 
      interests: SNK and RL are employees of BASF SE and AN is employee of Givaudan SA, 
      both companies use the described DA to develop and register substances.
EDAT- 2020/06/21 06:00
MHDA- 2021/03/26 06:00
CRDT- 2020/06/21 06:00
PHST- 2020/01/29 00:00 [received]
PHST- 2020/06/04 00:00 [revised]
PHST- 2020/06/07 00:00 [accepted]
PHST- 2020/06/21 06:00 [pubmed]
PHST- 2021/03/26 06:00 [medline]
PHST- 2020/06/21 06:00 [entrez]
AID - S0273-2300(20)30139-2 [pii]
AID - 10.1016/j.yrtph.2020.104713 [doi]
PST - ppublish
SO  - Regul Toxicol Pharmacol. 2020 Aug;115:104713. doi: 10.1016/j.yrtph.2020.104713. 
      Epub 2020 Jun 17.