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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
Toxicology in Vitro ( IF 2.6 ) Pub Date : 2020-10-08 , DOI: 10.1016/j.tiv.2020.105017
William Masinja 1 , Claire Elliott 2 , Sandeep Modi 3 , Steven J Enoch 4 , Mark T D Cronin 4 , Elizabeth F McInnes 3 , Richard A Currie 3
Affiliation  

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.



中文翻译:

基因组过敏原快速检测 (GARD) 检测与哺乳动物检测在确定农业化学活性成分的皮肤致敏潜力方面的预测性质的比较

非常需要哺乳动物测试的替代方法来预测农业化学活性成分 (AI) 的皮肤致敏潜力。GARD 检测是一种刺激的树突状细胞样细胞系,可测量基因组特征,使用 12 种 AI(7 种敏化剂和 5 种非敏化剂)进行评估,并将结果与​​豚鼠或局部淋巴结检测 (LLNA) 的历史结果进行比较学习。最初的 GARD 结果表明 11/12 AI 是致敏物,有 6 种与哺乳动物数据一致。保形预测将一个 AI 更改为非敏感器。在 GARD 检测中被确定为非致敏的 AI 被认为是 LLNA 中的有效致敏剂。总共有 7/12 GARD 结果与哺乳动物数据相符。在适用领域方面,AI 化学可能无法与 GARD 训练集相提并论。虽然 GARD 检测可以取代哺乳动物对包括化妆品成分在内的化合物进行皮肤致敏性评估的测试,但需要在农业化学化学方面进一步开展工作,以使该检测成为动物测试的可行替代品。然而,这里进行的工作被认为是探索性研究,该方法需要进一步开发以验证农用化学品。用于 AI 监管安全评估的哺乳动物和其他替代检测方法必须为分配适当的人类健康保护分类提供信心。考虑的探索性研究和方法需要进一步开发以验证农用化学品。用于 AI 监管安全评估的哺乳动物和其他替代检测方法必须为分配适当的人类健康保护分类提供信心。考虑的探索性研究和方法需要进一步开发以验证农用化学品。用于 AI 监管安全评估的哺乳动物和其他替代检测方法必须为分配适当的人类健康保护分类提供信心。

更新日期:2020-10-15
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