PMID- 35502631
OWN - NLM
STAT- MEDLINE
DCOM- 20230119
LR  - 20230119
IS  - 1868-8551 (Electronic)
IS  - 1868-596X (Linking)
VI  - 40
IP  - 1
DP  - 2023
TI  - Exploration of the GARDskin applicability domain: Indirectly acting haptens, 
      hydrophobic substances and UVCBs.
PG  - 53-60
LID - 10.14573/altex.2201281 [doi]
AB  - Hazard assessments of skin sensitizers are increasingly performed using new 
      approach methodologies (NAMs), with several in chemico, in vitro, and most 
      recently, also defined approaches accepted for regulatory use. However, keeping 
      track of potential limitations of each method to define applicability domains 
      remains a crucial component to ensure adequate predictivity and to facilitate the 
      appropriate selection of method(s) for each hazard assessment task. The objective 
      of this report is to share test results generated with the GARDskin assay on 
      chemicals that have traditionally been considered difficult to test in some of 
      the conventional in vitro and in chemico OECD Test Guidelines for skin 
      sensitization. Such compounds may include, for example, indirectly acting 
      haptens, hydrophobic substances, and substances of unknown or variable 
      composition, complex reaction products or biological substances (UVCBs). Based on 
      the results of this study, the sensitivity for prediction of skin sensitizing 
      hazard of indirectly acting haptens was 92.4% and 87.5% when compared with local 
      lymph node assay (LLNA) (n = 25) and human data (n = 8), respectively. Similarly, 
      the sensitivity for prediction of skin sensitizing hazard of hydrophobic 
      substances was 85.1% and 100% when compared with LLNA (n = 24) and human data (n 
      = 9), respectively. Lastly, a case study involving assessment of a set of 
      hydrophobic UVCBs (n = 7) resulted in a sensitivity of 100% compared to available 
      reference data. These data provide support for the inclusion of such chemistries 
      in the GARDskin applicability domain without an increased risk of false negative 
      classifications.
FAU - Forreryd, Andy
AU  - Forreryd A
AD  - SenzaGen AB, Lund, Sweden.
FAU - Gradin, Robin
AU  - Gradin R
AD  - SenzaGen AB, Lund, Sweden.
FAU - Humfrey, Charles
AU  - Humfrey C
AD  - The Lubrizol Corporation, Derby, UK.
FAU - Sweet, Len
AU  - Sweet L
AD  - The Lubrizol Corporation, Wickliffe, OH, USA.
FAU - Johansson, Henrik
AU  - Johansson H
AD  - SenzaGen AB, Lund, Sweden.
LA  - eng
PT  - Journal Article
DEP - 20220421
PL  - Germany
TA  - ALTEX
JT  - ALTEX
JID - 100953980
RN  - 0 (Haptens)
RN  - 0 (Allergens)
SB  - IM
MH  - Humans
MH  - *Dermatitis, Allergic Contact/etiology
MH  - Haptens
MH  - Skin
MH  - Local Lymph Node Assay
MH  - Biological Assay
MH  - Allergens
OTO - NOTNLM
OT  - GARD skin sensitization applicability domain
OT  - GARDskin
OT  - difficult to test substances
EDAT- 2022/05/04 06:00
MHDA- 2023/01/20 06:00
CRDT- 2022/05/03 04:43
PHST- 2022/01/28 00:00 [received]
PHST- 2022/04/13 00:00 [accepted]
PHST- 2022/05/03 04:43 [entrez]
PHST- 2022/05/04 06:00 [pubmed]
PHST- 2023/01/20 06:00 [medline]
AID - 10.14573/altex.2201281 [doi]
PST - ppublish
SO  - ALTEX. 2023;40(1):53-60. doi: 10.14573/altex.2201281. Epub 2022 Apr 21.