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应用不良结局路径框架,使用新方法研究纳米材料的皮肤致敏潜力。

Application of the adverse outcome pathway framework for investigating skin sensitization potential of nanomaterials using new approach methods.

机构信息

Laboratory of Education and Research in in vitro Toxicology (Tox In), Faculty of Pharmacy, Universidade Federal de Goiás, Goiânia, Brazil.

Laboratory of Pharmaceutical Technology-Farmatec, Faculty of Pharmacy, Universidade Federal de Goiás, Goiânia, Brazil.

出版信息

Contact Dermatitis. 2021 Feb;84(2):67-74. doi: 10.1111/cod.13669. Epub 2020 Oct 5.

Abstract

BACKGROUND

Currently, considerable efforts to standardize methods for accurate assessment of properties and safety aspects of nanomaterials are being made. However, immunomodulation effects upon skin exposure to nanomaterial have not been explored.

OBJECTIVES

To investigate the immunotoxicity of single-wall carbon nanotubes, titanium dioxide, and fullerene using the current mechanistic understanding of skin sensitization by applying the concept of adverse outcome pathway (AOP).

METHODS

Investigation of the ability of nanomaterials to interact with skin proteins using the micro-direct peptide reactivity assay; the expression of CD86 cell surface marker using the U937 cell activation test (OECD No. 442E/2018); and the effects of nanomaterials on modulating inflammatory response through inflammatory cytokine release by U937 cells.

RESULTS

The nanomaterials easily internalized into keratinocytes cells, interacted with skin proteins, and triggered activation of U937 cells by increasing CD86 expression and modulating inflammatory cytokine production. Consequently, these nanomaterials were classified as skin sensitizers in vitro.

CONCLUSIONS

Our study suggests the potential immunotoxicity of nanomaterials and highlights the importance of studying the immunotoxicity and skin sensitization potential of nanomaterials to anticipate possible human health risks using standardized mechanistic nonanimal methods with high predictive accuracy. Therefore, it contributes toward the applicability of existing OECD (Organisation for Economic Co-operation and Development) testing guidelines for accurate assessment of nanomaterial skin sensitization potential.

摘要

背景

目前,人们正在努力标准化方法,以准确评估纳米材料的特性和安全方面。然而,纳米材料对皮肤的免疫调节作用尚未得到探索。

目的

应用不良结局途径(AOP)的概念,利用皮肤致敏的现有机制理解,研究单壁碳纳米管、二氧化钛和富勒烯的免疫毒性。

方法

使用微直接肽反应测定法研究纳米材料与皮肤蛋白相互作用的能力;使用 U937 细胞激活试验(经合组织编号 442E/2018)检测 CD86 细胞表面标记物的表达;通过 U937 细胞释放炎性细胞因子来研究纳米材料对调节炎症反应的影响。

结果

这些纳米材料很容易进入角质形成细胞,与皮肤蛋白相互作用,并通过增加 CD86 表达和调节炎性细胞因子的产生来触发 U937 细胞的激活。因此,这些纳米材料被分类为体外皮肤致敏剂。

结论

我们的研究表明纳米材料具有潜在的免疫毒性,并强调了研究纳米材料的免疫毒性和皮肤致敏潜力的重要性,以使用具有高预测准确性的标准化机制非动物方法来预测可能的人类健康风险。因此,这有助于提高现有经合组织(经济合作与发展组织)测试指南对纳米材料皮肤致敏潜力的评估准确性。

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