PMID- 37074977
OWN - NLM
STAT- MEDLINE
DCOM- 20231030
LR  - 20231030
IS  - 1868-8551 (Electronic)
IS  - 1868-596X (Linking)
VI  - 40
IP  - 4
DP  - 2023
TI  - Integrated skin sensitization assessment based on OECD methods (III): Adding 
      human data to the assessment.
PG  - 571-583
LID - 10.14573/altex.2302081 [doi]
AB  - Skin sensitizer potency assessment based on new approach methodologies is key to 
      deriving a point of departure (PoD) for risk assessment. Regression models to 
      predict a PoD based on OECD-validated in vitro tests and trained on local lymph 
      node assay (LLNA) data were previously presented, and results from human tests 
      were recently compiled. To integrate both data sources, the Reference Chemical 
      Potency List (RCPL), which provides potency values (PV) for 33 chemicals 
      integrating LLNA and human data in a structured weight-of-evidence approach, was 
      developed. When calculating regression models vs PV or LLNA data, different 
      weights for the input parameters were noted. As the RCPL is based on too few 
      chemicals to train robust statistical models, the list of human data was extended 
      to a larger set of PV (n = 139) with associated in vitro data. This database was 
      used to retrain the regression models and to compare regression models trained vs 
      (i) LLNA, (ii) PV or (iii) human DSA04 values. Using the PV as a target, 
      predictive models of similar predictivity to the LLNA-based models were obtained, 
      which mainly differ in a lesser weight of cytotoxicity and a higher weight of 
      cell activation and reactivity parameters. Analysis of the human DSA04 dataset 
      indicates a similar pattern but also shows that the human dataset is too small 
      and biased to be a key dataset for potency prediction. Hence, an enlarged set of 
      PV values appears to be a complementary tool to train predictive models next to 
      an LLNA-only database.
FAU - Natsch, Andreas
AU  - Natsch A
AD  - Fragrances S&T, Ingredients Research, Givaudan Schweiz AG, Kemptthal, 
      Switzerland.
LA  - eng
PT  - Journal Article
DEP - 20230417
PL  - Germany
TA  - ALTEX
JT  - ALTEX
JID - 100953980
RN  - 0 (Allergens)
SB  - IM
MH  - Humans
MH  - *Dermatitis, Allergic Contact
MH  - Organisation for Economic Co-Operation and Development
MH  - Local Lymph Node Assay
MH  - Databases, Factual
MH  - Models, Statistical
MH  - Skin
MH  - Allergens
OTO - NOTNLM
OT  - animal data
OT  - human data
OT  - in vitro testing
OT  - point of departure
OT  - potency
OT  - risk assessment
OT  - skin sensitization
EDAT- 2023/04/19 18:42
MHDA- 2023/10/30 06:46
CRDT- 2023/04/19 13:13
PHST- 2023/02/08 00:00 [received]
PHST- 2023/04/17 00:00 [accepted]
PHST- 2023/10/30 06:46 [medline]
PHST- 2023/04/19 18:42 [pubmed]
PHST- 2023/04/19 13:13 [entrez]
AID - 10.14573/altex.2302081 [doi]
PST - ppublish
SO  - ALTEX. 2023;40(4):571-583. doi: 10.14573/altex.2302081. Epub 2023 Apr 17.