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首页> 外文期刊>Journal of applied toxicology >A novel in chemico method to detect skin sensitizers in highly diluted reaction conditions
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A novel in chemico method to detect skin sensitizers in highly diluted reaction conditions

机译:在高稀释的反应条件下检测皮肤敏化剂的Chemico方法中的一种新型

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The direct peptide reactivity assay (DPRA) is a simple and versatile alternative method for the evaluation of skin sensitization that involves the reaction of test chemicals with two peptides. However, this method requires concentrated solutions of test chemicals, and hydrophobic substances may not dissolve at the concentrations required. Furthermore, hydrophobic test chemicals may precipitate when added to the reaction solution. We previously established a high-sensitivity method, the amino acid derivative reactivity assay (ADRA). This method uses novel cysteine (NAC) and novel lysine derivatives (NAL), which were synthesized by introducing a naphthalene ring to the amine group of cysteine and lysine residues. In this study, we modified the ADRA method by reducing the concentration of the test chemicals 100-fold. We investigated the accuracy of skin sensitization predictions made using the modified method, which was designated the ADRA-dilutional method (ADRA-DM). The predictive accuracy of the ADRA-DM for skin sensitization was 90% for 82 test chemicals which were also evaluated via the ADRA, and the predictive accuracy in the ADRA-DM was higher than that in the ADRA and DPRA. Furthermore, no precipitation of test compounds was observed at the initiation of the ADRA-DM reaction. These results show that the ADRA-DM allowed the use of test chemicals at concentrations two orders of magnitude lower than that possible with the ADRA. In addition, ADRA-DM does not have the restrictions on test compound solubility that were a major problem with the DPRA. Therefore, the ADRA-DM is a versatile and useful method. Copyright (c) 2015 John Wiley & Sons, Ltd.
机译:直接肽反应性测定(DPRA)是一种简单而通用的替代方法,用于评估皮肤致敏,涉及试验化学品与两种肽的反应。然而,该方法需要浓缩的测试化学品溶液,疏水性物质可能不会以所需的浓度溶解。此外,当加入到反应溶液中时,疏水性测试化学品可能沉淀。我们以前建立了一种高灵敏度方法,氨基酸衍生物反应性测定(ADRA)。该方法采用新型半胱氨酸(NAC)和新型赖氨酸衍生物(NAL),其通过将萘环引入半胱氨酸和赖氨酸残基的胺基而合成。在这项研究中,我们通过降低测试化学品100倍的浓度来修改ADRA方法。我们研究了使用改性方法制备的皮肤致敏预测的准确性,该方法被指定为ADRA-稀释方法(ADRA-DM)。 82个测试化学品的ADRA-DM的预测精度为82个测试化学品,也通过ADRA评估,ADRA-DM的预测精度高于ADRA和DPRA。此外,在ADRA-DM反应的开始时没有观察到测试化合物的沉淀。这些结果表明,ADRA-DM允许在浓度下使用试验化学品,比ADRA低的两个数量级低。此外,ADRA-DM没有对测试复合溶解度的限制,这是DPRA的主要问题。因此,ADRA-DM是一种多功能和有用的方法。版权所有(c)2015 John Wiley&Sons,Ltd。

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