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基于高通量筛选(HTS)的分光光度直接肽反应性测定法(Spectro-DPRA)预测人体皮肤致敏潜能。

High-throughput screening (HTS)-based spectrophotometric direct peptide reactivity assay (Spectro-DPRA) to predict human skin sensitization potential.

机构信息

Safety and Microbiology Lab, Safety and Regulatory Research Division, AmorePacific Corporation R&D Unit, Yongin-si, South Korea; Department of Laboratory Animal Medicine, Research Institute for Veterinary Science, BK21 PLUS Program for Creative Veterinary Science Research, College of Veterinary Medicine, Seoul National University, Seoul 08826, South Korea.

Safety and Microbiology Lab, Safety and Regulatory Research Division, AmorePacific Corporation R&D Unit, Yongin-si, South Korea.

出版信息

Toxicol Lett. 2019 Oct 10;314:27-36. doi: 10.1016/j.toxlet.2019.07.014. Epub 2019 Jul 8.

DOI:10.1016/j.toxlet.2019.07.014
PMID:31295538
Abstract

Some cosmetic ingredients can act as a chemical hapten to induce an immune response; therefore, evaluating the sensitizing potential of cosmetic ingredients is essential. We previously developed a novel in chemico direct peptide reactivity assay involving a spectrophotometric evaluation (Spectro-DPRA) for animal skin sensitization tests (local lymph node assay; LLNA). Based on previous research, we expanded the test materials to confirm the effectiveness of the Spectro-DPRA method for predicting the animal skin sensitization potential, and further determined the feasibility of the method for estimating the human skin sensitization potential. Spectro-DPRA showed 83.1% or 89.1% accuracy compared to a conventional LLNA or prediction based on human data, respectively, with a combination model using both a cysteine peptide and lysine peptide cut-off. To identify the effect of the lipophilicity of a chemical on predicting the skin sensitization potential, we applied our prediction model to chemicals with a Log P range of -1 to 4. Overall predictability was increased, and the accuracy compared to the LLNA and human data was 91.5% and 94.9%, respectively, in the combination cut-off prediction model. In conclusion, Spectro-DPRA serves as an easy, rapid, and high-throughput in chemico screening method with high accuracy to predict the human skin sensitization potential of chemicals.

摘要

一些化妆品成分可以作为化学半抗原,引发免疫反应;因此,评估化妆品成分的致敏潜力至关重要。我们之前开发了一种新的化学直接肽反应性测定法,涉及分光光度评价(分光-DPRA),用于动物皮肤致敏试验(局部淋巴结试验;LLNA)。基于先前的研究,我们扩展了测试材料,以确认 Spectro-DPRA 方法预测动物皮肤致敏潜力的有效性,并进一步确定该方法估计人类皮肤致敏潜力的可行性。与传统的 LLNA 或基于人类数据的预测相比,Spectro-DPRA 的准确率分别为 83.1%或 89.1%,使用胱氨酸肽和赖氨酸肽截断的组合模型。为了确定化学物质的亲脂性对预测皮肤致敏潜力的影响,我们将我们的预测模型应用于 Log P 范围为-1 到 4 的化学物质。在组合截断预测模型中,整体可预测性提高,与 LLNA 和人类数据的准确性分别为 91.5%和 94.9%。总之,Spectro-DPRA 是一种简单、快速、高通量的化学筛选方法,具有很高的准确性,可以预测化学品对人类皮肤的致敏潜力。

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