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Masinja, W, Elliott, C, Modi, S, Enoch, SJ, Cronin, MTD, McInnes, EF and Currie, RA (2020) 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. Toxicology In Vitro. ISSN 0887-2333
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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..pdf - Accepted Version Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (1MB) | Preview |
Abstract
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.
| Item Type: | Article |
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| Uncontrolled Keywords: | 1115 Pharmacology and Pharmaceutical Sciences |
| Subjects: | R Medicine > RM Therapeutics. Pharmacology |
| Divisions: | Pharmacy & Biomolecular Sciences |
| Publisher: | Elsevier |
| Date Deposited: | 12 Oct 2020 11:28 |
| Last Modified: | 08 Oct 2021 00:50 |
| DOI or ID number: | 10.1016/j.tiv.2020.105017 |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/13824 |
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