一种用于体外皮肤刺激性测试的新型重建人表皮。

A new reconstructed human epidermis for in vitro skin irritation testing.

作者信息

Pedrosa Tatiana do Nascimento, Catarino Carolina Motter, Pennacchi Paula Comune, Assis Sílvia Romano de, Gimenes Fabrícia, Consolaro Márcia Edilaine Lopes, Barros Silvia Berlanga de Moraes, Maria-Engler Silvya Stuchi

机构信息

Clinical Chemistry & Toxicology Department, School of Pharmaceutical Sciences, University of São Paulo, Av. Professor Lineu Prestes, 580, Bloco 17, 05508-000 São Paulo, SP, Brazil.

Department of Clinical Analysis and Biomedicine, State University of Maringá, Avenida Colombo, 5790, CEP, 87020-900 Maringá, Paraná, Brazil.

出版信息

Toxicol In Vitro. 2017 Aug;42:31-37. doi: 10.1016/j.tiv.2017.03.010. Epub 2017 Mar 23.

Abstract

Different models of reconstructed human epidermis (RHE) are currently validated to assess skin irritation in vitro and ultimately to the animal replacement of the Draize test. The development of a new RHE model is a challenge for many laboratories, representing a potential gain of autonomy and improvement of technological knowledge. The Organization for Economic Co-operation and Development (OECD) encourages the development of new models and, for this purpose, offers a thorough guideline on quality control parameters (OECD TG 439 performance standards). This work aimed to develop an RHE model (i.e. USP-RHE) for in vitro skin irritation assays, following the OECD TG 439. The developed model presents a well-differentiated epidermis similar to the Validated Reference Methods (VRM) and to native human epidermis. Quality parameters, i.e. optical density of negative control, tissue integrity and barrier function, were similar to VRM and in accordance with OECD TG 439. Moreover, the USP-RHE model was shown to have 85,7% of specificity (6/7), 100% of sensitivity (6/6) and 92,3% of accuracy (12/13) when compared to in vivo UN GHS classification. The within-laboratory reproducibility was 92.3% (12/13). Thus, we demonstrated that USP-RHE model attends to all OECD TG 439 performance standards and is ready to be used by private and public laboratories and companies for future validation studies.

摘要

目前,不同的重建人表皮(RHE)模型已得到验证,可用于体外评估皮肤刺激性,并最终替代Draize试验中的动物实验。开发一种新的RHE模型对许多实验室来说都是一项挑战,这代表着自主性的潜在提升和技术知识的进步。经济合作与发展组织(OECD)鼓励开发新模型,并为此提供了关于质量控制参数的全面指南(OECD TG 439性能标准)。这项工作旨在按照OECD TG 439开发一种用于体外皮肤刺激性试验的RHE模型(即USP-RHE)。所开发的模型呈现出与验证参考方法(VRM)和天然人表皮相似的高度分化的表皮。质量参数,即阴性对照的光密度、组织完整性和屏障功能,与VRM相似且符合OECD TG 439。此外,与体内联合国全球化学品统一分类和标签制度(GHS)分类相比,USP-RHE模型的特异性为85.7%(6/7),敏感性为100%(6/6),准确性为92.3%(12/13)。实验室内的重现性为92.3%(12/13)。因此,我们证明了USP-RHE模型符合所有OECD TG 439性能标准,可供公共和私人实验室及公司用于未来的验证研究。

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