Comparative assessment of 24-hr primary skin irritation test and human patch test data with in vitro skin irritation tests according to OECD Test Guideline 439 (for quasi-drugs in Japan).

根据 OECD 测试指南 439 （ 日本的准药物 ） ， 对 24 小时原发性皮肤刺激测试和人体斑点测试数据与体外皮肤刺激测试的比较评估。

• 影响指数: 1.792
• 发表时间: 2018
• 来源期刊: J Toxicol Sci
• DOI: 10.2131/jts.43.751
• PMID: 30518713
• 文章类型: Comparative Study
• 中科院分区: Q4
• 方向: 医学
• 作者列表: Sugiyama M,Akita M,Alépée N,Fujishiro M,Hagino S,Handa Y,Ikeda H,Imai N,Jitsukawa S,Katoh M,Kurihara K,Kyotani D,Nomura S,Okamoto Y,Okumura H,Omori T,Sugibayashi K,Todo H,Toyoda A,Ohno Y

关键词: 24-hr Human patch test; In vitro; OECD TG 439; Quasi-drugs; Reconstructed human epidermis; Skin irritation

Mesh: Animal Testing Alternatives; Animals; Humans; Irritants / toxicity; Organisation for Economic Co-Operation and Development; Patch Tests; Rabbits; Skin Irritancy Tests

Abstract

The Organisation for Economic Co-operation and Development (OECD) Test Guideline (TG) 439 is an in vitro test method of reconstructed human epidermis (RhE), which was developed for hazard identification of irritating chemicals in accordance with a primary skin irritation test using rabbits with 4-hr exposure. A regulation for quasi-drugs in Japan requires data from primary skin irritation tests using rabbits to undergo 24-hr exposure, and this is used as an evidence for 24-hr closed patch tests in humans. In this study with the same chemicals, primary skin irritation test data using rabbits undergoing 24-hr exposure and a 24-hr occlusive human patch test data were analyzed by comparing the results obtained with four test methods adopted in OECD TG 439. The performances of in vitro test methods showed a positive predictive value of 72.7-85.7% to predict the results of 24-hr primary rabbit skin irritation test knowing that its positive predictive value was 57.1% against humans only. The prediction factors of in vitro test methods were higher for the human patch test data with a sensitivity reaching 60 to 80%. Three surfactants gave false negatives in some of the RhE methods evaluated with the human patch test, but in each case, they were correctly classified as positive when evaluated at double concentration. Therefore, the approach of setting the margin to 2 was effective in eliminating false negatives. This suggests that in vitro test methods are useful for assessing skin irritation potential without animal testing for the application of quasi-drugs in Japan.

摘要

经济合作与发展组织（OECD）测试指南（TG）439是一种重建人表皮（RhE）的体外测试方法，根据使用4小时暴露的兔子进行的主要皮肤刺激测试，开发用于刺激性化学物质的危害识别。日本对准药物的规定要求使用兔子进行24小时暴露的主要皮肤刺激试验的数据，这被用作人类24小时封闭斑贴试验的证据。在这项使用相同化学物质的研究中，通过比较OECDTG439中采用的四种测试方法获得的结果，分析了使用兔子进行24小时暴露的主要皮肤刺激测试数据和24小时闭塞性人类斑贴测试数据。体外测试方法的性能显示出72.7-85.7％的阳性预测值，以预测24小时原代兔皮肤刺激测试的结果，因为其阳性预测值仅对人类为57.1％。体外测试方法的预测因子对于人类斑贴测试数据较高，灵敏度达到60％至80％。在用人类斑贴试验评估的某些RhE方法中，三种表面活性剂产生假阴性，但是在每种情况下，当在双重浓度下评估时,它们被正确地分类为阳性.因此,将边距设置为2的方法有效地消除了假阴性。这表明体外测试方法可用于评估皮肤刺激潜力，而无需在日本进行准药物应用的动物测试。