PMID- 34247252
OWN - NLM
STAT- MEDLINE
DCOM- 20211027
LR  - 20211027
IS  - 1868-8551 (Electronic)
IS  - 1868-596X (Linking)
VI  - 38
IP  - 4
DP  - 2021
TI  - A triangular approach for the validation of new approach methods for skin 
      sensitization.
PG  - 669-677
LID - 10.14573/altex.2105111 [doi]
AB  - The availability of reference data is a key requirement for the development of 
      new approach methods (NAM), i.e., in vitro, in chemico and in silico methods and 
      integrated approaches, like defined approaches (DA), which combine these data 
      sources. Reference data are of even greater importance for regulatory acceptance. 
      In contrast to most other adverse effects, human skin sensitization data on many 
      chemicals are available, next to data from animal studies, such as the local 
      lymph node assay (LLNA). Skin sensitization NAM data can therefore be compared to 
      different reference datasets. Recent publications and validation at the OECD 
      focused on human and LLNA reference data. The "2 out of 3" DA (2o3 DA) is the 
      first DA for skin sensitization solely based on experimental data from validated 
      tests and was recently adopted as an OECD test guideline. Here we review the 
      predictivity of the 2o3 DA on multiple human and LLNA reference datasets. 
      Concomitantly, we compare the predictivity of the LLNA for human data within the 
      same datasets. Comparing predictivity of methods not only bilaterally (NAM or DA 
      vs. animal method) but including human data in a triangle "NAM data - animal data 
      - human data" offers a comprehensive assessment of the NAM's and DA's 
      predictivity. In all these assessments, the 2o3 DA was superior to the LLNA in 
      predicting human skin sensitization hazard. This highlights the importance of a 
      holistic view of reference data instead of limiting validation of NAMs and DAs to 
      data from a single animal test only.
FAU - Natsch, Andreas
AU  - Natsch A
AD  - Fragrances S&T, Ingredients Research, Givaudan Schweiz AG, Kemptthal, 
      Switzerland.
FAU - Landsiedel, Robert
AU  - Landsiedel R
AD  - BASF SE Experimental Toxicology and Ecology, Ludwigshafen, Germany.
FAU - Kolle, Susanne N
AU  - Kolle SN
AD  - BASF SE Experimental Toxicology and Ecology, Ludwigshafen, Germany.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20210708
PL  - Germany
TA  - ALTEX
JT  - ALTEX
JID - 100953980
SB  - IM
MH  - *Animal Testing Alternatives
MH  - Animals
MH  - Computer Simulation
MH  - *Dermatitis, Allergic Contact
MH  - Humans
MH  - Local Lymph Node Assay
MH  - Skin
OTO - NOTNLM
OT  - "2 out of 3" defined approach
OT  - defined approach
OT  - human data
OT  - reference data
OT  - skin sensitization
EDAT- 2021/07/12 06:00
MHDA- 2021/10/28 06:00
CRDT- 2021/07/11 20:58
PHST- 2021/05/11 00:00 [received]
PHST- 2021/07/07 00:00 [accepted]
PHST- 2021/07/11 20:58 [entrez]
PHST- 2021/07/12 06:00 [pubmed]
PHST- 2021/10/28 06:00 [medline]
AID - 10.14573/altex.2105111 [doi]
PST - ppublish
SO  - ALTEX. 2021;38(4):669-677. doi: 10.14573/altex.2105111. Epub 2021 Jul 8.