PMID- 33038465
OWN - NLM
STAT- MEDLINE
DCOM- 20210916
LR  - 20210916
IS  - 1879-3177 (Electronic)
IS  - 0887-2333 (Linking)
VI  - 70
DP  - 2021 Feb
TI  - Comparison of the predictive nature of the Genomic Allergen Rapid Detection 
      (GARD) assay with mammalian assays in determining the skin sensitisation 
      potential of agrochemical active ingredients.
PG  - 105017
LID - S0887-2333(20)30567-1 [pii]
LID - 10.1016/j.tiv.2020.105017 [doi]
AB  - Alternatives to mammalian testing are highly desirable to predict the skin 
      sensitisation potential of agrochemical active ingredients (AI). The GARD assay, 
      a stimulated, dendritic cell-like, cell line measuring genomic signatures, was 
      evaluated using twelve AIs (seven sensitisers and five non-sensitisers) and the 
      results compared with historical results from guinea pig or local lymph node 
      assay (LLNA) studies. Initial GARD results suggested 11/12 AIs were sensitisers 
      and six concurred with mammalian data. Conformal predictions changed one AI to a 
      non-sensitiser. An AI identified as non-sensitising in the GARD assay was 
      considered a potent sensitiser in the LLNA. In total 7/12 GARD results 
      corresponded with mammalian data. AI chemistries might not be comparable to the 
      GARD training set in terms of applicability domains. Whilst the GARD assay can 
      replace mammalian tests for skin sensitisation evaluation for compounds including 
      cosmetic ingredients, further work in agrochemical chemistries is needed for this 
      assay to be a viable replacement to animal testing. The work conducted here is, 
      however, considered exploratory research and the methodology needs further 
      development to be validated for agrochemicals. Mammalian and other alternative 
      assays for regulatory safety assessments of AIs must provide confidence to assign 
      the appropriate classification for human health protection.
CI  - Copyright (c) 2020 Elsevier Ltd. All rights reserved.
FAU - Masinja, William
AU  - Masinja W
AD  - Syngenta, International Research Centre, Jealott's Hill, Bracknell, Berks RG42 
      6EY, United Kingdom; School of Pharmacy and Biomolecular Sciences, Liverpool John 
      Moores University, Byrom Street, Liverpool L3 3AF, United Kingdom. Electronic 
      address: william.masinja@syngenta.com.
FAU - Elliott, Claire
AU  - Elliott C
AD  - Syngenta, International Research Centre, Jealott's Hill, Bracknell, Berks RG42 
      6EY, United Kingdom; Penman Consulting Limited, Aspect House, Waylands Avenue, 
      Wantage, Oxon OX12 9FF, United Kingdom.
FAU - Modi, Sandeep
AU  - Modi S
AD  - Syngenta, International Research Centre, Jealott's Hill, Bracknell, Berks RG42 
      6EY, United Kingdom.
FAU - Enoch, Steven J
AU  - Enoch SJ
AD  - School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, 
      Byrom Street, Liverpool L3 3AF, United Kingdom.
FAU - Cronin, Mark T D
AU  - Cronin MTD
AD  - School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, 
      Byrom Street, Liverpool L3 3AF, United Kingdom.
FAU - McInnes, Elizabeth F
AU  - McInnes EF
AD  - Syngenta, International Research Centre, Jealott's Hill, Bracknell, Berks RG42 
      6EY, United Kingdom.
FAU - Currie, Richard A
AU  - Currie RA
AD  - Syngenta, International Research Centre, Jealott's Hill, Bracknell, Berks RG42 
      6EY, United Kingdom.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20201008
PL  - England
TA  - Toxicol In Vitro
JT  - Toxicology in vitro : an international journal published in association with 
      BIBRA
JID - 8712158
RN  - 0 (Agrochemicals)
RN  - 0 (Allergens)
RN  - 0 (Haptens)
SB  - IM
MH  - Agrochemicals/*toxicity
MH  - Allergens/*toxicity
MH  - Animal Testing Alternatives
MH  - Animals
MH  - Biological Assay/*methods
MH  - Cell Line, Tumor
MH  - Dermatitis, Allergic Contact
MH  - Genomics/*methods
MH  - Guinea Pigs
MH  - Haptens/*toxicity
MH  - Humans
MH  - Mice
MH  - Skin/drug effects
MH  - Skin Tests/*methods
OTO - NOTNLM
OT  - Agrochemicals
OT  - Chemical domain
OT  - GARD assay
OT  - Mammalian testing
OT  - Skin sensitisation prediction
EDAT- 2020/10/11 06:00
MHDA- 2021/09/18 06:00
CRDT- 2020/10/10 20:09
PHST- 2020/07/20 00:00 [received]
PHST- 2020/09/25 00:00 [revised]
PHST- 2020/10/05 00:00 [accepted]
PHST- 2020/10/11 06:00 [pubmed]
PHST- 2021/09/18 06:00 [medline]
PHST- 2020/10/10 20:09 [entrez]
AID - S0887-2333(20)30567-1 [pii]
AID - 10.1016/j.tiv.2020.105017 [doi]
PST - ppublish
SO  - Toxicol In Vitro. 2021 Feb;70:105017. doi: 10.1016/j.tiv.2020.105017. Epub 2020 
      Oct 8.