PMID- 35404469
OWN - NLM
STAT- MEDLINE
DCOM- 20221102
LR  - 20221102
IS  - 1868-8551 (Electronic)
IS  - 1868-596X (Linking)
VI  - 39
IP  - 4
DP  - 2022
TI  - Integrated skin sensitization assessment based on OECD methods (I): Deriving a 
      point of departure for risk assessment.
PG  - 636-646
LID - 10.14573/altex.2201141 [doi]
AB  - Three guidelines covering key events in the skin sensitization adverse outcome 
      pathway are endorsed by the Organisation for Economic Co-operation and 
      Development (OECD). A recent guideline covers defined approaches (DA) to combine 
      data from these tests for regulatory (sub)classification. The guideline methods 
      provide continuous data that could charac-terize the sensitization potency on a 
      more granular scale beyond (sub)classifications. We assembled a comprehensive 
      database of in vitro and in vivo results from OECD guideline tests. Building on a 
      previous approach using regression models, we provide quantitative models using 
      input data from the kinetic direct peptide reactivity assay (kDPRA), the 
      KeratinoSens (KS) assay, and the human cell line activation test (h-CLAT) to 
      calculate a point of departure (PoD) in the form of a predicted local lymph node 
      assay (LLNA) EC3 value for use in risk assessment. Predictive models include 
      results from either two or all three assays. Detailed analysis versus in vivo 
      data estimates redundancy between different tests and helps guide model 
      selection. All models were tested on a set of case studies selected for their 
      availability of multiple LLNA reference data in the OECD database. The predicted 
      PoDs were within or close to the range of the variation of the historical LLNA 
      data for most of these cases studies, and overall, the models predicted the in 
      vivo value with a median fold-misprediction factor of around 2.5. The robustness 
      of the models was characterized by comparing a comprehensive historical database 
      versus the curated dataset provided by the OECD working group on DA.
FAU - Natsch, Andreas
AU  - Natsch A
AD  - Fragrances S&T, Ingredients Research, Givaudan Schweiz AG, Kemptthal, 
      Switzerland.
FAU - Gerberick, George Frank
AU  - Gerberick GF
AD  - GF3 Consultancy, LLC, Cincinnati, OH, USA.
LA  - eng
PT  - Journal Article
DEP - 20220411
PL  - Germany
TA  - ALTEX
JT  - ALTEX
JID - 100953980
SB  - IM
MH  - Animals
MH  - Humans
MH  - *Animal Testing Alternatives/methods
MH  - Organisation for Economic Co-Operation and Development
MH  - *Dermatitis, Allergic Contact
MH  - Local Lymph Node Assay
MH  - Skin
MH  - Risk Assessment
OTO - NOTNLM
OT  - in vitro testing
OT  - point of departure
OT  - potency risk assessment
OT  - skin sensitization
EDAT- 2022/04/12 06:00
MHDA- 2022/11/03 06:00
CRDT- 2022/04/11 12:15
PHST- 2022/01/14 00:00 [received]
PHST- 2022/03/15 00:00 [accepted]
PHST- 2022/04/11 12:15 [entrez]
PHST- 2022/04/12 06:00 [pubmed]
PHST- 2022/11/03 06:00 [medline]
AID - 10.14573/altex.2201141 [doi]
PST - ppublish
SO  - ALTEX. 2022;39(4):636-646. doi: 10.14573/altex.2201141. Epub 2022 Apr 11.