GARD™皮肤试验:金属适用领域的研究。

IF 4.5 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Andy Forreryd, Robin Gradin, Olivia Larne, Nissanka Rajapakse, Eliot Deag, Henrik Johansson
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引用次数: 1

摘要

在过去十年中,经合组织采用了皮肤致敏化学品危害识别的新方法方法(NAMs)作为测试指南。这些动物模型的替代方案与皮肤致敏不良结果通路(AOP)中的单个关键事件(KE)一致,其中分子起始事件(MIE)与蛋白质共价结合。就目前而言,AOP不包括金属致敏的机制事件,并且关于NAMs是否准确预测此类分子的致敏潜力的信息有限,这些分子已被提出通过替代有机化学物质的机制起作用。评估金属致敏潜势的方法将是支持风险管理的宝贵工具,例如,在新金属盐生产过程中的职业环境中,或在医疗器械行业中,以评估金属合金的可浸出物。本文描述了GARD™皮肤测定法用于金属评估的适用性领域的系统评估。危害分类补充了金属致敏剂诱导的基因表达谱的扩展分析,以比较金属和有机致敏剂对毒性途径的诱导。根据本研究结果,GAR-D™皮肤预测皮肤致敏危害的准确性、敏感性和特异性分别为92%(12/13)、100%(7/7)和83%(5/6)。因此,GARD™蒙皮用于评估金属的性能被发现与观察到的传统有机物质相似,为在测试方法的适用范围内包含金属提供了支持。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The GARD™skin assay: Investigation of the applicability domain for metals.

New approach methodologies (NAMs) for hazard identification of skin sensitizing chemicals were adopted as test guidelines by the OECD during the last decade. These alternatives to animal models align to individual key events (KE) in the adverse outcome pathway (AOP) for skin sensitization for which the molecular initiating event (MIE) is covalent binding to proteins. As it currently stands, the AOP does not include mechanistic events of sensitization by metals, and limited information is available on whether NAMs accurately predict the sensitization potential of such molecules, which have been proposed to act via alternative mechanisms to organic chemicals. Methods for assessing the sensitization potential of metals would be valuable tools to support risk management within, e.g., occupational settings during production of new metal salts or within the medical device industry to evaluate leachables from metal alloys. This paper describes a systematic evaluation of the applicability domain of the GARD™skin assay for the assessment of metals. Hazard classifications were supplemented with an extended analysis of gene expression profiles induced by metal sensitizers to compare the induction of toxicity pathways between metals and organic sensitizers. Based on the results of this study, the accuracy, sensitivity, and specificity of GAR­D™skin for the prediction of skin sensitizing hazard were 92% (12/13), 100% (7/7), and 83% (5/6), respectively. Thus, the performance of GARD™skin for the assessment of metals was found to be similar to that observed for conventional organic substances, providing support for inclusion of metals within the applicability domain of the test method.

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来源期刊
Altex-Alternatives To Animal Experimentation
Altex-Alternatives To Animal Experimentation MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
7.70
自引率
8.90%
发文量
89
审稿时长
2 months
期刊介绍: ALTEX publishes original articles, short communications, reviews, as well as news and comments and meeting reports. Manuscripts submitted to ALTEX are evaluated by two expert reviewers. The evaluation takes into account the scientific merit of a manuscript and its contribution to animal welfare and the 3R principle.
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